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_001354304.2:c.1176dup

CA1139768925

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: fd3c60ab-667c-460a-a5f3-592256fb7342

HGVS expressions

NM_001354304.2:c.1176dup

NC_000012.12:g.102843672dup

CM000674.2:g.102843672dup

NC_000012.11:g.103237450dup

CM000674.1:g.103237450dup

NC_000012.10:g.101761580dup

NG_008690.1:g.78934dup

NG_008690.2:g.119742dup

ENST00000553106.6:c.1176dup

ENST00000307000.7:c.1161dup

ENST00000549247.6:n.935dup

ENST00000551114.2:n.838dup

ENST00000553106.5:c.1176dup

ENST00000635477.1:n.280dup

ENST00000635528.1:n.691dup

NM_000277.1:c.1176dup

NM_000277.2:c.1176dup

NM_001354304.1:c.1176dup

NM_000277.3:c.1176dup

Pathogenic

PVS1 PM3_Supporting PP4 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The nonsense variant c.1176dup (p.Asn393Ter) occurs in exon 11 and is predicted to result in NMD. The variant is absent from population databases. At least one classical PKU patient has been reported (PMID: 20188615) homozygous for this variant. In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3_supporting, PP4.

PVS1

The c.1176dup (p.Asn393Ter) nonsense variant is in exon 11 is predicted to result in NMD.

PM3_Supporting

The proband of Family 2 in PMID: 20188615 is homozygous for the c.1176dup (reported as c.1177insT). 0.5pt

PP4

The proband of Family 2 in PMID: 20188615 has classic PKU with serum Phe level of 1619 umol/l. Exclusion of BH4 deficiency was not reported.

PM2

The variant is absent from gnomAD, ExAC, 1000 Genomes, and ESP.

Approved on: 2022-07-30

Published on: 2022-07-30

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