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_000277.2(PAH):c.1068C>A (p.Tyr356Ter)

CA273107

92729 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6f390ad4-1675-4f3f-9b2d-eb81f608dc3b

HGVS expressions

NM_000277.2:c.1068C>A

NM_000277.2(PAH):c.1068C>A (p.Tyr356Ter)

NC_000012.12:g.102843777G>T

CM000674.2:g.102843777G>T

NC_000012.11:g.103237555G>T

CM000674.1:g.103237555G>T

NC_000012.10:g.101761685G>T

NG_008690.1:g.78826C>A

NG_008690.2:g.119634C>A

NM_000277.1:c.1068C>A

NM_001354304.1:c.1068C>A

NM_000277.3:c.1068C>A

ENST00000307000.7:c.1053C>A

ENST00000549247.6:n.827C>A

ENST00000551114.2:n.730C>A

ENST00000553106.5:c.1068C>A

ENST00000635477.1:n.172C>A

ENST00000635528.1:n.583C>A

Pathogenic

PM3_Strong PM2 PVS1 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PVS1: Nonsense variant; PM2: gnomAD MAF 0.00017; PP4_Moderate: Detected in PKU patients (PMID:25894915); PM3_Strong: in trans with p.W326X (Pathogenic), and IVS4-1G>A (Pathogenic). (PMID:25894915). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PVS1, PM2, PP4_Moderate, PM3_Strong).

PM3_Strong

in trans with p.W326X (Pathogenic), and IVS4-1G>A (Pathogenic).

Identified in several patients in this cohort in trans with p.W326X (Pathogenic), p.R158W, p.G257V, and IVS4-1G>A (Pathogenic). PubMed:25894915

PM2

gnomAD MAF 0.00017

PVS1

Nonsense variant

PP4_Moderate

Detected in PKU patients

BH4 defect excluded in all patients PubMed:25894915

Approved on: 2018-08-13

Published on: 2019-04-06

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