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_001354304.2:c.1316-1G>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA386492906

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 915d6c96-324f-40b3-85d7-bb533737c9cb

Approved on: 2022-12-09

Published on: 2022-12-09

HGVS expressions

NM_001354304.2:c.1316-1G>C

NC_000012.12:g.102839219C>G

CM000674.2:g.102839219C>G

NC_000012.11:g.103232997C>G

CM000674.1:g.103232997C>G

NC_000012.10:g.101757127C>G

NG_008690.1:g.83384G>C

NG_008690.2:g.124192G>C

ENST00000553106.6:c.1316-1G>C

ENST00000307000.7:c.1301-1G>C

ENST00000551114.2:n.978-1G>C

ENST00000553106.5:c.1316-1G>C

ENST00000635477.1:n.420-1G>C

ENST00000635528.1:n.831-1G>C

NM_000277.1:c.1316-1G>C

NM_000277.2:c.1316-1G>C

NM_001354304.1:c.1316-1G>C

NM_000277.3:c.1316-1G>C

Likely Pathogenic

PVS1_Strong PM3 PM2 PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This variant c.1316-1G>C in PAH was detected in a patient with classic PKU with the pathogenic variant p.Arg243Gln (PMID: 28982351). This variant was absent in population databases. This is a canonical variant in the -1 splice acceptor of intron 12; this would alter a region that is critical to protein function with nonsense mediated decay not predicted. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1_Strong, PM2, PM3, PP4.

PVS1_Strong

Canonical variant not predicted to undergo NMD. It occurs in the -1 splice acceptor site of the IVS12 results in exon skipping or use of a cryptic splice site that disrupts the reading frame. Located in exon 13 and removes <10% of protein. This is predicted to alter a region that is critical to protein function.

PM3

This variant was detected in trans with the pathogenic variant p.Arg243Gln in a patient with cPKU (PMID:28982351). points=1.

PM2

This variant is absent from population databases gnomAD and ExAC

PP4

Variant was detected in a patient with cPKU. BH4 cofactor deficiency assessed using the loading test. PMID: 228982351

Curation History

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