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

CA16020940

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b55a6542-48d2-4198-bcf1-7b9c2bb3dce4

HGVS expressions

NM_000277.3:c.1103A>G

ENST00000553106.6:c.1103A>G

ENST00000307000.7:c.1088A>G

ENST00000549247.6:n.862A>G

ENST00000551114.2:n.765A>G

ENST00000553106.5:c.1103A>G

ENST00000635477.1:n.207A>G

ENST00000635528.1:n.618A>G

NM_000277.1:c.1103A>G

NM_000277.2:c.1103A>G

NM_001354304.1:c.1103A>G

NM_001354304.2:c.1103A>G

NC_000012.12:g.102843742T>C

CM000674.2:g.102843742T>C

NC_000012.11:g.103237520T>C

CM000674.1:g.103237520T>C

NC_000012.10:g.101761650T>C

NG_008690.1:g.78861A>G

NG_008690.2:g.119669A>G

Uncertain Significance

PM2

PP4 PP3 PM5 PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1103A>G (p.Glu368Gly) variant in PAH has been reported in an Indian family with an affected patient with classical PKU. BH4 deficiency not reportedly ruled out. The patient is deceased and was not available for genotyping, but each parent was a heterozygous carrier of this variant. (PMID: 24130151) This variant is absent from 1000G, ESP, ExAC and gnomAD. Computational evidence is conflicting. The p.Glu368Lys variant is interpreted as Pathogenic by 1 submitter in ClinVar, and as likely pathogenic by PAH VCEP. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2.

PM2

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

PP4

Reported in a deceased patient with classical PKU. BH4 deficiency not reportedly ruled out. PMID: 24130151

PP3

Computational evidence is conflicting: Deleterious in SIFT, MutationTaster; Benign in PolyPhen2, REVEL=0.724.

PM5

p.Glu368Lys interpreted as Pathogenic by 1 submitter, Interpreted as likely pathogenic by PAH VCEP

PM3

Parents were heterozygous carriers PMID: 24130151

Approved on: 2021-05-28

Published on: 2021-05-28

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