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_000277.3(PAH):c.1232C>A (p.Ser411Ter)

CA229409

102574 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

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

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

PVS1 PM2

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)

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).

PM2

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

Approved on: 2022-12-09

Published on: 2022-12-09

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