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)

CA229300

102491 (ClinVar)

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

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

Approved on: 2020-04-13

Published on: 2020-04-13

HGVS expressions

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

NM_000277.1:c.1046C>A

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

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 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

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).

PM2

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

Curation History

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