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]

Variant: NM_000277.3(PAH):c.1232C>A (p.Ser411Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229409

102574 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 76b8ca65-6f27-43cd-b05c-0179c6f3f851

Approved on: 2022-12-09

Published on: 2022-12-09

HGVS expressions

NM_000277.3:c.1232C>A

NM_000277.3(PAH):c.1232C>A (p.Ser411Ter)

NC_000012.12:g.102840483G>T

CM000674.2:g.102840483G>T

NC_000012.11:g.103234261G>T

CM000674.1:g.103234261G>T

NC_000012.10:g.101758391G>T

NG_008690.1:g.82120C>A

NG_008690.2:g.122928C>A

ENST00000553106.6:c.1232C>A

ENST00000307000.7:c.1217C>A

ENST00000551114.2:n.894C>A

ENST00000553106.5:c.1232C>A

ENST00000635477.1:n.336C>A

ENST00000635528.1:n.747C>A

NM_000277.1:c.1232C>A

NM_000277.2:c.1232C>A

NM_001354304.1:c.1232C>A

NM_001354304.2:c.1232C>A

Likely Pathogenic

PM2 PVS1

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The NM_000277.3(PAH):c.1232C>A (p.Ser411Ter) variant in exon 12 of PAH is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 12/13 and is predicted to lead to nonsense mediated decay (PVS1). This variant is absent from gnomAD v2.1.1 (PM2). The variant has been reported in one patient in PMID: 17935162 however additional phenotype and genotype information was not specified. In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive phenylketonuria based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH VCEP: PVS1, PM2. (PAH VCEP specifications version 1)

PM2

This variant is absent from gnomAD v2.1.1 (PM2).

PVS1

The c.1232C>A (p.Ser411Ter) variant in exon 12 of PAH is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 12/13 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.