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

CA16020885

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 25d719d3-4100-4594-bc0b-e40e47da828c

HGVS expressions

NM_000277.3:c.886G>C

NC_000012.12:g.102851713C>G

CM000674.2:g.102851713C>G

NC_000012.11:g.103245491C>G

CM000674.1:g.103245491C>G

NC_000012.10:g.101769621C>G

NG_008690.1:g.70890G>C

NG_008690.2:g.111698G>C

NM_000277.1:c.886G>C

NM_000277.2:c.886G>C

NM_001354304.1:c.886G>C

ENST00000307000.7:c.871G>C

ENST00000549247.6:n.645G>C

ENST00000551114.2:n.548G>C

ENST00000553106.5:c.886G>C

ENST00000635477.1:n.47G>C

Uncertain Significance

PM2 PP3 PP4_Moderate

PM3 PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.886G>C (p.Asp296His) variant in PAH has been reported in a PKU patient from mainland China, BH4 deficiency assessed (PMID: 26503515). A change to glycine at the same codon has been observed associated with phenylketonuria. This variant is absent from 1000G, ESP, and gnomAD databases. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.949. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP3, PM2, PP4_moderate.

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

REVEL score 0.949

PP4_Moderate

Detected in 1 PKU patient from China. BH4 deficiency assessed. PMID: 26503515

PM3

See paper below

PM5

The alternate missense (p.Asp296Gly) is not established pathogenic, though in ClinVar.

Approved on: 2019-07-14

Published on: 2019-07-14

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