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_000277.3(PAH):c.850T>C (p.Cys284Arg)

CA229822

102878 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f2c506ad-64eb-4609-9b6b-1f13c72a3465

Approved on: 2019-12-08

Published on: 2021-04-09

HGVS expressions

NM_000277.3:c.850T>C

NM_000277.3(PAH):c.850T>C (p.Cys284Arg)

NC_000012.12:g.102851749A>G

CM000674.2:g.102851749A>G

NC_000012.11:g.103245527A>G

CM000674.1:g.103245527A>G

NC_000012.10:g.101769657A>G

NG_008690.1:g.70854T>C

NG_008690.2:g.111662T>C

ENST00000307000.7:c.835T>C

ENST00000553106.5:c.850T>C

NM_000277.1:c.850T>C

NM_000277.2:c.850T>C

NM_001354304.1:c.850T>C

NM_001354304.2:c.850T>C

Likely Pathogenic

PP4_Moderate PM3 PM2 PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.850T>C (p.Cys284Arg) variant in PAH has been reported in 1 individual with classic PKU (BH4 deficiency excluded). (PP4_Moderate; PMID: 30050108). This variant is absent in population databases (PM2). This variant was detected in trans with pathogenic variant p.EX6-96A>G (VarID590; PM3). Computational evidence predicts a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3, PP3.

PP4_Moderate

reported in a patient with classic PKU, BH4 deficiency ruled out PMID: 30050108

PM3

detected in trans with p.EX6-96A>G (VarID590, P, 4 submitters)

PM2

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

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster. REVEL=0.903

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