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

CA16020903

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0208bdeb-de85-440c-b8f0-3da6b7188eda

HGVS expressions

NM_000277.1:c.949T>C

NM_000277.2:c.949T>C

NM_001354304.1:c.949T>C

NM_000277.3:c.949T>C

NM_001354304.2:c.949T>C

ENST00000307000.7:c.934T>C

ENST00000549247.6:n.708T>C

ENST00000551114.2:n.611T>C

ENST00000553106.5:c.949T>C

ENST00000635477.1:n.74-2484T>C

ENST00000635528.1:n.464T>C

NC_000012.12:g.102846915A>G

CM000674.2:g.102846915A>G

NC_000012.11:g.103240693A>G

CM000674.1:g.103240693A>G

NC_000012.10:g.101764823A>G

NG_008690.1:g.75688T>C

NG_008690.2:g.116496T>C

Uncertain Significance

PM2

PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The NM_000277.3:c.949T>C (p.Tyr317His) variant is a missense variant in exon 9/13 of PAH. The variant does not appear to have been reported in the published literature (as of 07/02/2020). The variant is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). The variant is predicted damaging by multiple in-silico missense predictors, including REVEL (REVEL score 0.983), but tolerated by SIFT, such that PP3 is not met. Classification: VUS – insufficient evidence Supporting Criteria: PM2

PM2

Not found in any pop database

PP3

SIFT predicts variant is tolerated. PolyPhen and MutTaster predict damaging. REVEL=0.865. PP3 not met

Approved on: 2020-07-25

Published on: 2020-07-25

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.