{"_id":"chr12:g.103248964A>G","_version":2,"cadd":{"_license":"http://bit.ly/2TIuab9","alt":"G","anc":"A","annotype":"CodingTranscript","bstatistic":809,"chmm":{"bivflnk":0.0,"enh":0.008,"enhbiv":0.0,"het":0.031,"quies":0.787,"reprpc":0.008,"reprpcwk":0.126,"tssa":0.0,"tssaflnk":0.0,"tssbiv":0.0,"tx":0.008,"txflnk":0.0,"txwk":0.024,"znfrpts":0.0},"chrom":12,"consdetail":"missense","consequence":"NON_SYNONYMOUS","consscore":7,"cpg":0.01,"dna":{"helt":-0.19,"mgw":0.27,"prot":2.49,"roll":1.67},"encode":{"exp":7.57,"h3k27ac":4.28,"h3k4me1":2.76,"h3k4me3":3.0,"nucleo":1.4},"exon":"6/13","fitcons":0.65045,"gc":0.43,"gene":{"ccds_id":"CCDS9092.1","cds":{"cdna_pos":1129,"cds_pos":656,"rel_cdna_pos":0.27,"rel_cds_pos":0.48},"feature_id":"ENST00000553106","gene_id":"ENSG00000171759","genename":"PAH","prot":{"domain":"ndomain","protpos":219,"rel_prot_pos":0.48}},"gerp":{"n":5.47,"rs":683.5,"rs_pval":2.62852e-107,"s":5.47},"grantham":155,"isderived":"TRUE","isknownvariant":"FALSE","istv":"FALSE","length":0,"mapability":{"20bp":1,"35bp":1},"min_dist_tse":94,"min_dist_tss":62034,"mutindex":0,"naa":"S","oaa":"F","phast_cons":{"mammalian":0.999,"primate":0.953,"vertebrate":1.0},"phred":31,"phylop":{"mammalian":2.085,"primate":0.525,"vertebrate":3.282},"polyphen":{"cat":"probably_damaging","val":0.939},"pos":103248964,"rawscore":6.524233,"ref":"A","segway":"R2","sift":{"cat":"deleterious","val":0.01},"type":"SNV"},"chrom":"12","clinvar":{"_license":"http://bit.ly/2SQdcI0","allele_id":920580,"alt":"G","chrom":"12","cytogenic":"12q23.2","gene":{"id":"5053","symbol":"PAH"},"hg19":{"end":103248964,"start":103248964},"hg38":{"end":102855186,"start":102855186},"hgvs":{"coding":["NM_000277.3:c.656T>C","NM_001354304.2:c.656T>C"],"genomic":["NC_000012.11:g.103248964A>G","NC_000012.12:g.102855186A>G","NG_008690.2:g.108225T>C"],"protein":["NP_000268.1:p.Phe219Ser","NP_001341233.1:p.Phe219Ser"]},"rcv":{"accession":"RCV001200012","clinical_significance":"Uncertain significance","conditions":{"identifiers":{"medgen":"C0031485","mondo":"MONDO:0009861","omim":"261600","orphanet":"716"},"name":"Phenylketonuria (PKU)","synonyms":["FOLLING DISEASE","OLIGOPHRENIA PHENYLPYRUVICA","Phenylketonurias"]},"last_evaluated":"2020-03-07","number_submitters":1,"origin":"germline","preferred_name":"NM_000277.3(PAH):c.656T>C (p.Phe219Ser)","review_status":"reviewed by expert panel"},"ref":"A","rsid":"rs1164279708","type":"single nucleotide variant","variant_id":932275},"dbnsfp":{"_license":"http://bit.ly/2VLnQBz","aa":{"alt":"S","codon_degeneracy":[0,0],"codonpos":[2,2],"pos":[219,214],"ref":"F","refcodon":["TTC","TTC"]},"alphamissense":{"pred":["P","P"],"rankscore":0.86921,"score":[0.9072,0.9501]},"alt":"G","altai_neandertal":["A","A"],"ancestral_allele":"A","appris":"principal1","bayesdel":{"add_af":{"pred":"D","rankscore":0.9184,"score":0.436252},"no_af":{"pred":"D","rankscore":0.91739,"score":0.38887}},"bstatistic":{"converted_rankscore":0.73785,"score":528.0},"chagyrskaya_neandertal":["A","A"],"chrom":"12","clinpred":{"pred":"D","rankscore":0.82166,"score":0.99181866645813},"clinvar":{"clinvar_id":"932275","clnsig":"Uncertain_significance","hgvs":"NC_000012.12:g.102855186A>G","medgen":"C0031485","omim":"261600","orphanet":"716","review":"reviewed_by_expert_panel","trait":"Phenylketonuria"},"dann":{"rankscore":0.95892,"score":0.9988297446022708},"denisova":["A","A"],"deogen2":{"pred":["D","D"],"rankscore":0.99987,"score":[0.9945,0.830381]},"eigen":{"phred_coding":7.287773,"raw_coding":0.711841807753943,"raw_coding_rankscore":0.80407},"eigen-pc":{"phred_coding":7.503572,"raw_coding":0.686313034389223,"raw_coding_rankscore":0.81338},"ensembl":{"geneid":["ENSG00000171759","ENSG00000171759"],"proteinid":["ENSP00000448059","ENSP00000303500"],"transcriptid":["ENST00000553106","ENST00000307000"]},"esm1b":{"pred":"D","rankscore":0.6933,"score":-9.256},"eve":{"class10_pred":"U","class20_pred":"U","class25_pred":"U","class30_pred":"U","class40_pred":"U","class50_pred":"U","class60_pred":"U","class70_pred":"U","class75_pred":"U","class80_pred":"U","class90_pred":"P","rankscore":0.67803,"score":0.6104664645399467},"fathmm":{"converted_rankscore":0.99697,"pred":["D","D"],"score":[-6.45,-6.45]},"fathmm-mkl":{"coding_group":"AEFBI","coding_pred":"D","coding_rankscore":0.61553,"coding_score":0.94557},"fathmm-xf":{"coding_pred":"D","coding_rankscore":0.90333,"coding_score":0.924782},"fitcons":{"gm12878":{"confidence_value":0,"rankscore":0.26702,"score":0.573888},"h1-hesc":{"confidence_value":0,"rankscore":0.51672,"score":0.653264},"huvec":{"confidence_value":0,"rankscore":0.26826,"score":0.564101},"integrated":{"confidence_value":0,"rankscore":0.43195,"score":0.638212}},"gencode_basic":["Y","Y"],"genename":["PAH","PAH"],"genocanyon":{"rankscore":0.24401,"score":0.81372838035282},"gerp":{"91_mammals":{"rankscore":0.29603,"score":1.05}},"gerp++":{"nr":5.47,"rs":5.47,"rs_rankscore":0.80345},"gmvp":{"rankscore":0.98166,"score":0.981744056345785},"hg18":{"end":101773094,"start":101773094},"hg19":{"end":103248964,"start":103248964},"hg38":{"end":102855186,"start":102855186},"hgvsc":["c.641T>C","c.656T>C"],"hgvsp":["p.F219S","p.F214S","p.Phe214Ser","p.Phe219Ser"],"interpro":{"domain":["Aromatic amino acid hydroxylase, C-terminal|Aromatic amino acid hydroxylase, C-terminal","Aromatic amino acid hydroxylase, C-terminal|Aromatic amino acid hydroxylase, C-terminal"]},"list-s2":{"pred":["D","D"],"rankscore":0.55382,"score":[0.860614,0.860614]},"lrt":{"converted_rankscore":0.8433,"omega":0.050062,"pred":"D","score":0.0},"m-cap":{"pred":"D","rankscore":0.98667,"score":0.828147},"metalr":{"pred":"D","rankscore":0.99463,"score":0.9824},"metarnn":{"pred":["D","D"],"rankscore":0.96924,"score":[0.97271246,0.97271246]},"metasvm":{"pred":"D","rankscore":0.9825,"score":1.0561},"mpc":{"rankscore":0.29513,"score":0.269893928028},"mutationassessor":{"pred":"M","rankscore":0.70756,"score":2.44},"mutationtaster":{"aae":["F219S","F214S"],"converted_rankscore":0.58761,"model":["simple_aae","simple_aae"],"pred":["D","D"],"score":[0.99998,0.999997]},"mutformer":{"rankscore":0.92387,"score":0.92917496},"mutpred":{"aa_change":"F219S","accession":"P00439","pred":{"mechanism":"Gain of disorder","p_val":0.0069},"rankscore":0.85673,"score":0.722},"mvp":{"rankscore":0.97591,"score":[0.97616573547,0.97616573547]},"phactboost":{"rankscore":0.94516,"score":0.998485005943567},"phastcons":{"100way_vertebrate":{"rankscore":0.71638,"score":1.0},"17way_primate":{"rankscore":0.678,"score":0.992},"470way_mammalian":{"rankscore":0.68203,"score":1.0}},"phylop":{"100way_vertebrate":{"rankscore":0.67085,"score":5.568},"17way_primate":{"rankscore":0.94297,"score":0.756},"470way_mammalian":{"rankscore":0.91505,"score":11.274}},"polyphen2":{"hdiv":{"pred":"D","rankscore":0.67487,"score":0.995},"hvar":{"pred":"D","rankscore":0.65394,"score":0.918}},"primateai":{"pred":"T","rankscore":0.59231,"score":0.64469230175},"provean":{"converted_rankscore":0.84742,"pred":["D","D"],"score":[-5.35,-5.35]},"ref":"A","reliability_index":10,"revel":{"rankscore":0.97248,"score":[0.901,0.901]},"rsid":"rs1164279708","sift":{"converted_rankscore":0.63226,"pred":["D","D"],"score":[0.005,0.005]},"sift4g":{"converted_rankscore":0.72224,"pred":["D","D"],"score":[0.005,0.005]},"siphy_29way":{"logodds_rankscore":0.36701,"logodds_score":9.2484,"pi":{"a":0.7253,"c":0.0,"g":0.0,"t":0.2747}},"tsl":[1,5],"uniprot":[{"acc":"P00439","entry":"PH4H_HUMAN"},{"acc":"J3KND8","entry":"J3KND8_HUMAN"}],"varity":{"er":{"rankscore":0.91767,"score":0.8539202},"er_loo":{"rankscore":0.90174,"score":0.8298205},"r":{"rankscore":0.93764,"score":0.9252533},"r_loo":{"rankscore":0.95145,"score":0.93898714}},"vep_canonical":"YES","vest4":{"rankscore":0.88687,"score":[0.878,0.888]},"vindijia_neandertal":["A","A"]},"dbsnp":{"_license":"http://bit.ly/2AqoLOc","alleles":[{"allele":"A","freq":{"dbgap_popfreq":1.0,"gnomad_exomes":1.0,"tommo":1.0,"topmed":1.0}},{"allele":"G","freq":{"tommo":0.0}},{"allele":"T","freq":{"dbgap_popfreq":0.0,"gnomad_exomes":0.0,"topmed":0.0}}],"alt":"G","chrom":"12","dbsnp_build":156,"gene":{"geneid":5053,"is_pseudo":false,"name":"phenylalanine hydroxylase","rnas":[{"codon_aligned_transcript_change":{"deleted_sequence":"TTC","inserted_sequence":"TTC","position":768,"seq_id":"NM_000277.3"},"hgvs":"NM_000277.3:c.656=","protein":{"variant":{"spdi":{"deleted_sequence":"F","inserted_sequence":"F","position":218,"seq_id":"NP_000268.1"}}},"protein_product":{"refseq":"NP_000268.1"},"refseq":"NM_000277.3","so":[{"accession":"SO:0001580","name":"coding_sequence_variant"}]},{"codon_aligned_transcript_change":{"deleted_sequence":"TTC","inserted_sequence":"TTC","position":996,"seq_id":"NM_001354304.2"},"hgvs":"NM_001354304.2:c.656=","protein":{"variant":{"spdi":{"deleted_sequence":"F","inserted_sequence":"F","position":218,"seq_id":"NP_001341233.1"}}},"protein_product":{"refseq":"NP_001341233.1"},"refseq":"NM_001354304.2","so":[{"accession":"SO:0001580","name":"coding_sequence_variant"}]},{"codon_aligned_transcript_change":{"deleted_sequence":"TTC","inserted_sequence":"TTC","position":768,"seq_id":"XM_017019370.2"},"hgvs":"XM_017019370.2:c.656=","protein":{"variant":{"spdi":{"deleted_sequence":"F","inserted_sequence":"F","position":218,"seq_id":"XP_016874859.1"}}},"protein_product":{"refseq":"XP_016874859.1"},"refseq":"XM_017019370.2","so":[{"accession":"SO:0001580","name":"coding_sequence_variant"}]}],"strand":"-","symbol":"PAH"},"hg19":{"end":103248964,"start":103248964},"ref":"A","rsid":"rs1164279708","vartype":"snv"},"hg19":{"end":103248964,"start":103248964},"observed":true,"snpeff":{"_license":"http://bit.ly/2suyRKt","ann":{"cdna":{"length":"2681","position":"1129"},"cds":{"length":"1359","position":"656"},"effect":"missense_variant","feature_id":"NM_000277.1","feature_type":"transcript","gene_id":"PAH","genename":"PAH","hgvs_c":"c.656T>C","hgvs_p":"p.Phe219Ser","protein":{"length":"452","position":"219"},"putative_impact":"MODERATE","rank":"6","total":"13","transcript_biotype":"protein_coding"}},"vcf":{"alt":"G","position":"103248964","ref":"A"}}