12:103234234:C/A
GRCh37/hg19 position 12:103234234
GRCh38/hg38 position 12:102840456
Alleles (ref/alt) C/A
dbSNP rsid rs767075719
Gene symbol

PAH

Most severe consequence missense_variant
Flanking sequence AAGCTGCTGGGTATTGTCCAAGACCTCAATC[C/A]TTTGGGTGTATGGGTCGTAGCGAACTGAGAA
HGVS

NM_000277.3:c.1259G>T

NM_001354304.2:c.1259G>T

NP_000268.1:p.Arg420Met

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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.1259G>T p.Arg420Met Exon 12
NM_001354304.2 PAH 14 missense_variant c.1259G>T p.Arg420Met 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
ExAC ALL 1 121344 0 0.000008
FIN 0 6614 0 0
NFE 1 66722 0 0.000015
EAS 0 8654 0 0
SAS 0 16510 0 0
AFR 0 10406 0 0
AMR 0 11530 0 0
OTH 0 908 0 0
gnomAD exomes ALL 2 246220 0 8.12282e-06
FIN 0 22300 0 0
NFE 2 111696 0 1.79057e-05
ASJ 0 9850 0 0
EAS 0 17248 0 0
SAS 0 30782 0 0
AFR 0 15302 0 0
AMR 0 33560 0 0
OTH 0 5482 0 0
Functional predictions
Tool Score Prediction
SIFT 0.013 damaging
Polyphen2 HDIV 0.997 probably damaging
Polyphen2 HVAR 0.87 possibly damaging
LRT 0.000000 deleterious
MutationTaster 1 disease_causing
MutationAssessor 2.14 medium
FATHMM -6.19 damaging
MetaSVM 1.0838 damaging
MetaLR 0.978 damaging
PROVEAN -1.02 neutral
M-CAP 0.792995 damaging
CADD 4.310764 -
REVEL 0.835 -
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 0.561 Conserved
phyloP46way placental 2.664 Conserved
phyloP100way vertebrates 5.363 Conserved
ClinVar
Accession Clinical significance Date last evaluated Review status Method Disease name Disease symbol Disease inheritance Pubmed
RCV001200002 Likely pathogenic 2020-05-21 reviewed by expert panel clinical testing Phenylketonuria PKU Autosomal recessive inheritance

30674554

28492532

27121329

35281663

23500595

25741868

32668217

27243974

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: Uncertain significance
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 Arg (R) Met (M)
Amino acid name Arginine Methionine
Side chain class basic sulfur-containing
Polarity basic polar nonpolar
Charge (pH=7.4) positively charged neutrally charged
Hydropathy hydrophilic moderate
Molecular weight 174.203 149.208
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).