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.510-1G>C

CA386297078

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: dc29e523-7eb6-4517-9b82-76db803126ed

HGVS expressions

NM_001354304.2:c.510-1G>C

NC_000012.12:g.102855333C>G

CM000674.2:g.102855333C>G

NC_000012.11:g.103249111C>G

CM000674.1:g.103249111C>G

NC_000012.10:g.101773241C>G

NG_008690.1:g.67270G>C

NG_008690.2:g.108078G>C

ENST00000553106.6:c.510-1G>C

ENST00000307000.7:c.495-1G>C

ENST00000549111.5:n.606-1G>C

ENST00000551988.5:n.531-1G>C

ENST00000553106.5:c.510-1G>C

NM_000277.1:c.510-1G>C

NM_000277.2:c.510-1G>C

NM_001354304.1:c.510-1G>C

NM_000277.3:c.510-1G>C

Pathogenic

PVS1 PP4 PM2 PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.510-1G>C variant in PAH was detected in a patient with PKU with the pathogenic variant p.Arg111Ter (PMID: 28982351). This variant was absent in population databases. This is a canonical variant in the -1 splice acceptor of intron 5. Exon skipping or use of a cryptic splice site would disrupt reading frame with nonsense mediated decay predicted. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4.

PVS1

Canonical variant predicted to undergo NMD. It occurs in the -1 splice acceptor site of the IVS5 results in exon skipping or use of a cryptic splice site. Located in intron 5 with 13 coding exons.

PP4

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

PM2

This variant is absent from population databases gnomAD and ExAC

PM3

This variant was detected in trans with the pathogenic variant p.Arg111* in a patient with mPKU (PMID:28982351). points=1.

Approved on: 2022-12-09

Published on: 2022-12-09

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