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_000277.1(PAH):c.1046C>A (p.Ser349Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229300

102491 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bc844832-84f0-4266-a9c8-5102faa58165

Approved on: 2020-04-13

Published on: 2020-04-13

HGVS expressions

NM_000277.1:c.1046C>A

NM_000277.1(PAH):c.1046C>A (p.Ser349Ter)

NC_000012.12:g.102844355G>T

CM000674.2:g.102844355G>T

NC_000012.11:g.103238133G>T

CM000674.1:g.103238133G>T

NC_000012.10:g.101762263G>T

NG_008690.1:g.78248C>A

NG_008690.2:g.119056C>A

NM_000277.2:c.1046C>A

NM_001354304.1:c.1046C>A

NM_000277.3:c.1046C>A

NM_001354304.2:c.1046C>A

ENST00000307000.7:c.1031C>A

ENST00000549247.6:n.805C>A

ENST00000551114.2:n.708C>A

ENST00000553106.5:c.1046C>A

ENST00000635477.1:n.150C>A

ENST00000635528.1:n.561C>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 c.1046C>A (p.Ser349Ter) variant in PAH is a null variant (nonsense variant) in exon 10 of 13 in a gene where LOF is a known mechanism of disease, leading to premature truncation and NMD (PVS1). It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). It has previously been reported in one classic PKU case per the BioPKU database (PMID: 24939588), without additional information. Classification: Likely Pathogenic Supporting criteria: PVS1, PM2

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PVS1

The c.976del (p.Trp326GlyfsTer15) variant in PAH is a null variant (frameshift variant) in a gene where LOF is a known mechanism of disease, leading to premature truncation and NMD (PVS1).

Curation History

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