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

CA16020782

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: cd016a2f-a812-4fe4-93a7-17220c514c1c

HGVS expressions

NM_000277.3:c.380A>G

NC_000012.12:g.102877523T>C

CM000674.2:g.102877523T>C

NC_000012.11:g.103271301T>C

CM000674.1:g.103271301T>C

NC_000012.10:g.101795431T>C

NG_008690.1:g.45080A>G

NG_008690.2:g.85888A>G

NM_000277.1:c.380A>G

NM_000277.2:c.380A>G

NM_001354304.1:c.380A>G

ENST00000307000.7:c.365A>G

ENST00000549111.5:n.476A>G

ENST00000550978.6:n.364A>G

ENST00000551337.5:c.380A>G

ENST00000551988.5:n.469A>G

ENST00000553106.5:c.380A>G

Uncertain Significance

PP3 PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.380A>G (p.Glu127Gly) variant in PAH has been reported in a Chinese patient with PAH deficiency (BH4 deficiency excluded) (PP4_Moderate; PMID: 26503515) This variant is absent from 1000G, ESP, ExAC and gnomAD (PM2). A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.896. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster. REVEL=0.896.

PM2

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

PP4_Moderate

Detected on 1 alelle. Diagnosed through neonatal screening program or by clinical presentation. Phenylalanine plasma concentrations >120 µmol/L were reported for all subjects. Tetrahydrobiopterin (BH4) deficiency was excluded through a BH4 loading test, urinary pterin analysis, DHPR activity assay. PMID: 26503515

PubMed:26503515

Approved on: 2019-11-17

Published on: 2019-11-17

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.