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12:103232972:G/T
GRCh37/hg19 position 12:103232972
GRCh38/hg38 position 12:102839194
Alleles (ref/alt) G/T
dbSNP rsid rs76542238
Gene symbol

PAH
Most severe consequence missense_variant
Flanking sequence CTGTCCATGGCTTTACTTTATTTTCTGGAGG[G/T]CACTGCAAAGGATTCCAATTTCACCTACAAA
HGVS

NM_000277.3:c.1340C>A

NM_001354304.2:c.1340C>A

NP_000268.1:p.Ala447Asp

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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.1340C>A p.Ala447Asp Exon 13
NM_001354304.2 PAH 14 missense_variant c.1340C>A p.Ala447Asp Exon 14
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
ExAC ALL 1 120896 0 0.000008
FIN 0 6600 0 0
NFE 1 66508 0 0.000015
EAS 0 8616 0 0
SAS 0 16474 0 0
AFR 0 10326 0 0
AMR 0 11464 0 0
OTH 0 908 0 0
gnomAD genomes ALL 1 30966 0 3.22935e-05
FIN 0 3490 0 0
NFE 1 15010 0 6.66223e-05
ASJ 0 302 0 0
EAS 0 1614 0 0
AFR 0 8730 0 0
AMR 0 838 0 0
OTH 0 982 0 0
gnomAD exomes ALL 2 245904 0 8.13326e-06
FIN 0 22262 0 0
NFE 2 111490 0 1.79388e-05
ASJ 0 9848 0 0
EAS 0 17244 0 0
SAS 0 30774 0 0
AFR 0 15282 0 0
AMR 0 33530 0 0
OTH 0 5474 0 0
Functional predictions
Tool Score Prediction
SIFT 0 damaging
Polyphen2 HDIV 0.998 probably damaging
Polyphen2 HVAR 0.976 probably damaging
LRT 0.000000 deleterious
MutationTaster 1 disease_causing
MutationAssessor 4.075 high
FATHMM -6.7 damaging
MetaSVM 0.9573 damaging
MetaLR 0.9932 damaging
PROVEAN -4.6 damaging
M-CAP 0.749822 damaging
CADD 4.308411 -
REVEL 0.963 -
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++ 5.31 Conserved
phastCons46way primates 0.981 Highly conserved
phastCons46way placental 0.995 Highly conserved
phastCons100way vertebrates 1.000 Highly conserved
phyloP46way primates 0.585 Conserved
phyloP46way placental 2.645 Conserved
phyloP100way vertebrates 6.878 Conserved
ClinVar
Accession Clinical significance Date last evaluated Review status Method Disease name Disease symbol Disease inheritance Pubmed
RCV000632880 Pathogenic 2022-09-12 criteria provided, multiple submitters, no conflicts clinical testing Phenylketonuria PKU -

9540801

12173030

8659548

10429004

28492532
RCV000088834 Pathogenic 2022-07-21 criteria provided, single submitter literature only not provided - - -
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 Ala (A) Asp (D)
Amino acid name Alanine Aspartic acid
Side chain class aliphatic acid
Polarity nonpolar acidic polar
Charge (pH=7.4) neutrally charged negatively charged
Hydropathy hydrophobic hydrophilic
Molecular weight 89.094 133.104
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).