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_000277.2(PAH):c.490A>G (p.Ile164Val)

CA229576

102698 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6daf45cd-bc30-4517-8391-4c64f38bea84

Approved on: 2018-08-13

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.490A>G

NM_000277.2(PAH):c.490A>G (p.Ile164Val)

NC_000012.12:g.102866615T>C

CM000674.2:g.102866615T>C

NC_000012.11:g.103260393T>C

CM000674.1:g.103260393T>C

NC_000012.10:g.101784523T>C

NG_008690.1:g.55988A>G

NG_008690.2:g.96796A>G

NM_000277.1:c.490A>G

NM_001354304.1:c.490A>G

NM_000277.3:c.490A>G

ENST00000307000.7:c.475A>G

ENST00000549111.5:n.586A>G

ENST00000551988.5:n.530+10847A>G

ENST00000553106.5:c.490A>G

Likely Pathogenic

PM3_Strong PP4_Moderate PM2

PP3

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PM2: ExAC MAF: 0.00012; PP4_Moderate: Detected in patients with PKU/HPA. BH4 deficiency excluded. (PMID:11244681; PMID:23942198); PM3_Strong: Detected with D145V, A403V (Pathogenic) (PMID:11244681; PMID:23942198). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP4_Moderate, PM3_Strong).

PM3_Strong

Detected with D145V, A403V (Pathogenic)

Patient/Sample 36: PAH variants: I164V and A403V (VarID 92731, Pathogenic) PubMed:23942198

Detected with D145V (VarID 102667, Pathogenic). PubMed:11244681

PP4_Moderate

Detected in patients with PKU/HPA. BH4 deficiency excluded.

All disease-causing mutations in PAH, GCH1, PTS, and QDPR were confirmed using Sanger sequencing or multiplex ligation-dependent probe amplification. Patient with HPA had 2 PAH mutations: I164V and A403V. PubMed:23942198

We evaluated the clinical data obtained from a multidisciplinary trial of 11 patients with PKU/HPA. I164V was identified in a patient with non-PKU HPA. PubMed:11244681

PM2

ExAC MAF: 0.00012

PP3

Conflicting predictions for pathogenicity

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.