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12:103234231:A/C
GRCh37/hg19 position 12:103234231
GRCh38/hg38 position 12:102840453
Alleles (ref/alt) A/C
dbSNP rsid -
Gene symbol

PAH
Most severe consequence missense_variant
Flanking sequence CTTAAGCTGCTGGGTATTGTCCAAGACCTCA[A/C]TCCTTTGGGTGTATGGGTCGTAGCGAACTGA
HGVS

NM_000277.3:c.1262T>G

NM_001354304.2:c.1262T>G

NP_000268.1:p.Ile421Ser

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Gene annotations
Transcript Gene Exon number Consequence HGVS cDNA HGVS protein Location Protein location
NM_000277.3 PAH 13 missense_variant c.1262T>G p.Ile421Ser Exon 12
NM_001354304.2 PAH 14 missense_variant c.1262T>G p.Ile421Ser Exon 13
Population frequency
Select populations: ALL LWK MKK YRI EUR FIN NFE CEU ASJ TSI EAS SAS CHB HAN CHD JPT AFR AMR ASW GIH MEX OTH
Database Population AC AN Hom AF
Functional predictions
Tool Score Prediction
SIFT 0 damaging
Polyphen2 HDIV 0.975 probably damaging
Polyphen2 HVAR 0.968 probably damaging
LRT 0.000023 deleterious
MutationTaster 0.999999 disease_causing
MutationAssessor 3.7 high
FATHMM -6.49 damaging
MetaSVM 0.9786 damaging
MetaLR 0.99 damaging
PROVEAN -4.98 damaging
M-CAP 0.732604 damaging
CADD 4.83728 -
REVEL 0.969 -
Conservation
Conservation scores are retrieved from UCSC genome browser. The conservation levels are defined by simple cutoff values. If the conservation levels do not agree with each other, you can manually check whether this variant is conserved with UCSC genome browser.
Method Score Level
GERP++ 5.33 Conserved
phastCons46way primates 0.997 Highly conserved
phastCons46way placental 0.997 Highly conserved
phastCons100way vertebrates 1 Highly conserved
phyloP46way primates 0.459 Not conserved
phyloP46way placental 2.152 Conserved
phyloP100way vertebrates 8.42 Conserved
ClinVar
Accession Clinical significance Date last evaluated Review status Method Disease name Disease symbol Disease inheritance Pubmed
RCV000792932 Likely pathogenic 2020-07-03 reviewed by expert panel curation Phenylketonuria PKU Autosomal recessive inheritance

28492532
InterVar

InterVar is a software tool for clinical interpretation of genetic variants by the ACMG/AMP 2015 guideline. The eveidence tags that variant met are highlighted. Please note that evidence tags with need to be evaluated manually.

Class: Likely pathogenic
Benign Pathogenic
Strong Supporting Supporting Moderate Strong Very Strong
Population data BA1
BS1
BS2 		PM2 PS4
Computational and predictive data BP1
BP3
BP4
BP7 		PP3 PM4
PM5		 PS1 PVS1
Functional data BS3 PP2 PM1 PS3
Segregation data BS4 PP1 PP1 PP1
De novo data PM6 PS2
Allelic data BP2 PM3
Other database BP6 PP5
Other data BP5 PP4
Amino acid change

The physichemical property of amino acid change.

Trait Ile (I) Ser (S)
Amino acid name Isoleucine Serine
Side chain class aliphatic hydroxyl-containing
Polarity nonpolar polar
Charge (pH=7.4) neutrally charged neutrally charged
Hydropathy hydrophobic hydrophilic
Molecular weight 131.175 105.093
gnomAD
The Genome Aggregation Database (gnomAD), is a coalition of investigators seeking to aggregate and harmonize exome and genome sequencing data from a variety of large-scale sequencing projects, and to make summary data available for the wider scientific community. In its first release, which contained exclusively exome data, it was known as the Exome Aggregation Consortium (ExAC).