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.1057del

CA16020923

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 18e44273-2216-4aa6-a268-686692947a3c

HGVS expressions

NM_001354304.2:c.1057del

NC_000012.12:g.102844344del

CM000674.2:g.102844344del

NC_000012.11:g.103238122del

CM000674.1:g.103238122del

NC_000012.10:g.101762252del

NG_008690.1:g.78259del

NG_008690.2:g.119067del

ENST00000553106.6:c.1057del

ENST00000307000.7:c.1042del

ENST00000549247.6:n.816del

ENST00000551114.2:n.719del

ENST00000553106.5:c.1057del

ENST00000635477.1:n.161del

ENST00000635528.1:n.572del

NM_000277.1:c.1057del

NM_000277.2:c.1057del

NM_001354304.1:c.1057del

NM_000277.3:c.1057del

Likely Pathogenic

PVS1 PM2

PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The frameshift variant c.1057del (p.Glu353AsnfsTer47) in exon 10 creates a premature stop codon in exon 11 which is predicted to result in NMD. The variant is absent from population databases, including gnomAD. One typical PKU patient has been reported (PMID: 8069318) which BioPKU reports affiliated with this variant however the actual variant is c.1055del, so no patients have been reported with this variant. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1 and PM2.

PVS1

The c.1057del (p.Glu353Asnfs*47) frameshift variant in exon 10 creates a premature stop codon in exon 11 which is predicted to result in NMD.

PM2

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

PP4

One typical PKU patient has been reported (PMID: 8069318) which BioPKU reports affiliated with this variant however the actual variant is c.1055del, so no patients have been reported with this variant.

Approved on: 2022-06-12

Published on: 2022-06-12

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