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]

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Variant: NM_000277.2(PAH):c.385G>T (p.Asp129Tyr)

CA286503

102660 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0d22d416-20d9-4abc-96d1-031831f71e57

Approved on: 2019-04-07

Published on: 2019-04-07

HGVS expressions

NM_000277.2:c.385G>T

NM_000277.2(PAH):c.385G>T (p.Asp129Tyr)

NC_000012.12:g.102877518C>A

CM000674.2:g.102877518C>A

NC_000012.11:g.103271296C>A

CM000674.1:g.103271296C>A

NC_000012.10:g.101795426C>A

NG_008690.1:g.45085G>T

NG_008690.2:g.85893G>T

NM_000277.1:c.385G>T

NM_001354304.1:c.385G>T

NM_000277.3:c.385G>T

ENST00000307000.7:c.370G>T

ENST00000549111.5:n.481G>T

ENST00000550978.6:n.369G>T

ENST00000551337.5:c.385G>T

ENST00000551988.5:n.474G>T

ENST00000553106.5:c.385G>T

Uncertain Significance

PP3 PM5 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.385G>T (p.Asp129Tyr) variant in PAH has not been reported in the literature to our knowledge. This variant is absent from 1000G, ESP, ExAC and gnomAD (PM2). Multiple lines of computational evidence support a deleterious effect (PP3). There are 2 other missense variants at this residue in ClinVar; p.Asp129Gly is Likely Pathogenic by 1 submitter and PAH EP (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3.

PP3

Multiple lines of computational evidence support a deleterious effect (SIFT, PolyPhen2, MutationTaster, REVEL=0.989

PM5

2 other missense variants at this residue in ClinVar: p.Asp129Gly LP by 1 submitter and PAH EP

PM2

Absent from ExAC/gnomAD, 1000 Genomes, ESP

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