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_001354304.2:c.311C>T

CA386304006

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bdfd24a5-2b03-45b5-9fee-9cc87e5acd76

HGVS expressions

NM_001354304.2:c.311C>T

NC_000012.12:g.102894776G>A

CM000674.2:g.102894776G>A

NC_000012.11:g.103288554G>A

CM000674.1:g.103288554G>A

NC_000012.10:g.101812684G>A

NG_008690.1:g.27827C>T

NG_008690.2:g.68635C>T

ENST00000553106.6:c.311C>T

ENST00000307000.7:c.296C>T

ENST00000546844.1:c.311C>T

ENST00000548928.1:n.233C>T

ENST00000549111.5:n.407C>T

ENST00000550978.6:n.295C>T

ENST00000551337.5:c.311C>T

ENST00000551988.5:n.400C>T

ENST00000553106.5:c.311C>T

NM_000277.1:c.311C>T

NM_000277.2:c.311C>T

NM_001354304.1:c.311C>T

NM_000277.3:c.311C>T

Likely Pathogenic

PM5 PP4_Moderate 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 c.311C>T (p.Ala104Val) missense variant in PAH has been reported in 1 Chinese patient with classic PKU (Phe >1200umol/L; BH4 deficiency excluded) (PMID: 29499199; PP4_Moderate). This variant is absent from population databases (PM2), and is located at same location a c.311C>A (p.Ala104Asp), reported as Pathogenic in ClinVar (VarID:102650). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM5.

PM5

At same location as NM_000277.3(PAH):c.311C>A (p.Ala104Asp); reported as Pathogenic in ClinVar (VarID:102650)

PP4_Moderate

PMID: 29499199 - A104V detected in 1 Chinese patient with CPKU (serum Phe >1200umol/L); BH4 deficiency excluded via urinary pterin analysis with HPLC

PM2

Variant absent from population databases.

PP3

Computational evidence is conflicting, predicted benign by by SIFT and PolyPhen2, predicted deleterious by MutationTaster, REVEL = 0.508

Approved on: 2022-07-30

Published on: 2022-07-30

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.