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

CA386296833

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 93378ff3-a0f5-476d-9386-3bbd7a51e0f0

HGVS expressions

NM_001354304.2:c.563G>T

NC_000012.12:g.102855279C>A

CM000674.2:g.102855279C>A

NC_000012.11:g.103249057C>A

CM000674.1:g.103249057C>A

NC_000012.10:g.101773187C>A

NG_008690.1:g.67324G>T

NG_008690.2:g.108132G>T

NM_000277.1:c.563G>T

NM_000277.2:c.563G>T

NM_001354304.1:c.563G>T

NM_000277.3:c.563G>T

ENST00000307000.7:c.548G>T

ENST00000549111.5:n.659G>T

ENST00000551988.5:n.584G>T

ENST00000553106.5:c.563G>T

Likely Pathogenic

PP3 PP4 PM3 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.563G>T (p.Gly188Val) variant in PAH was reported in trans with pathogenic variant p.Val399= in 1 patient with PAH deficiency (>120 μmol/L Phe) (PMID: 28982351). Computational evidence for this missense variant is predicted to be damaging (SIFT), probably damaging (PolyPhen2), and disease-causing (MutationTaster). This variant is absent from population databases gnomAD, 1000 Genomes, and ESP. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP3, PP4.

PP3

Damaging in SIFT, PolyPhen2 and MutationTaster

PP4

Detected in a patient with PAH deficiency (>120 μmol/L Phe). Patients with BH4 cofactor deficiency were excluded by BH4 loading. PMID: 28982351

PM3

Detected in trans with p.Val399= (P) 1.0pts PMID: 28982351

PM2

Absent from population databases gnomAD, 1000 Genomes and ESP.

Approved on: 2020-11-16

Published on: 2021-01-15

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