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.1076C>G (p.Ser359Ter)

CA229330

626 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 66e267b0-cf6d-463d-9f0e-6510e335ebb6

Approved on: 2020-06-26

Published on: 2020-06-26

HGVS expressions

NM_000277.3:c.1076C>G

NM_000277.3(PAH):c.1076C>G (p.Ser359Ter)

NM_000277.1:c.1076C>G

NM_000277.2:c.1076C>G

NM_001354304.1:c.1076C>G

NM_001354304.2:c.1076C>G

ENST00000307000.7:c.1061C>G

ENST00000549247.6:n.835C>G

ENST00000551114.2:n.738C>G

ENST00000553106.5:c.1076C>G

ENST00000635477.1:n.180C>G

ENST00000635528.1:n.591C>G

NC_000012.12:g.102843769G>C

CM000674.2:g.102843769G>C

NC_000012.11:g.103237547G>C

CM000674.1:g.103237547G>C

NC_000012.10:g.101761677G>C

NG_008690.1:g.78834C>G

NG_008690.2:g.119642C>G

Pathogenic

PP4_Moderate PM2 PVS1

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1076C>G (p.Ser359Ter) variant in PAH has been reported in an individual with PKU; BH4 deficiency excluded (PP4_Moderate; PMID: 8097261; (PMID: 9634518). This variant is absent in population databases (PM2). It is a nonsense variant in exon 11 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function (PVS1). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4_Moderate.

PP4_Moderate

S359X was identified in a PKU patient. PMID: 8097261; BH4 deficiency excluded as part of study inclusion criteria (PMID: 9634518)

PubMed:9634518

A new nonsense heterozygous C-->G transversion within exon 11 (S359X) was identified in a PKU patient. PubMed:8097261

PM2

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

PVS1

Nonsense variant in exon 11 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function

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