Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.3(PAH):c.523C>G (p.Pro175Ala)

CA229605

102722 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 532e385e-584f-4484-82d6-19b38c609ef7

HGVS expressions

NM_000277.3:c.523C>G

NM_000277.3(PAH):c.523C>G (p.Pro175Ala)

NC_000012.12:g.102855319G>C

CM000674.2:g.102855319G>C

NC_000012.11:g.103249097G>C

CM000674.1:g.103249097G>C

NC_000012.10:g.101773227G>C

NG_008690.1:g.67284C>G

NG_008690.2:g.108092C>G

NM_000277.1:c.523C>G

NM_000277.2:c.523C>G

NM_001354304.1:c.523C>G

ENST00000307000.7:c.508C>G

ENST00000549111.5:n.619C>G

ENST00000551988.5:n.544C>G

ENST00000553106.5:c.523C>G

Uncertain Significance

PM3_Supporting PP3 PP4 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.523C>G (p.Pro175Ala) variant in PAH has been reported in a US patient with MHP (PMID: 8659548). It was detected with pathogenic variant p.A104D. This variant is absent from population databases. A deleterious effect is predicted in multiple in silico models. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3_supporting, PP3.

PM3_Supporting

Detected with A104D (pathogenic 6 submitters) parental analysis not possible

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster, REVEL=0.91

PP4

Detected in a patient with MHP PMID: 8659548

PubMed:8659548

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, ESP

Approved on: 2020-01-30

Published on: 2020-01-31

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.