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]

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Variant: NM_001354304.2:c.669del

CA16020835

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 41f11bcf-264b-4292-9ef7-9ad4dd44f526

HGVS expressions

NM_001354304.2:c.669del

NC_000012.12:g.102855173del

CM000674.2:g.102855173del

NC_000012.11:g.103248951del

CM000674.1:g.103248951del

NC_000012.10:g.101773081del

NG_008690.1:g.67430del

NG_008690.2:g.108238del

ENST00000553106.6:c.669del

ENST00000307000.7:c.654del

ENST00000549111.5:n.765del

ENST00000553106.5:c.669del

NM_000277.1:c.669del

NM_000277.2:c.669del

NM_001354304.1:c.669del

NM_000277.3:c.669del

Pathogenic

PP4_Moderate PVS1 PM2_Supporting PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.669del (p.Asn223LysfsTer118) variant in PAH is a frameshift variant predicted to cause a premature stop codon in exon 6 leading to nonsense mediated decay. It was reported in a Chinese PKU patient with BH4 deficiency ruled out, in trans with pathogenic variant p.T278N (PMID: 24705691). It is absent in gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PP4_moderate, PM2_supporting, PM3.

PP4_Moderate

Detected in a PKU patient, PAH, PTS, GCH1, QDPR, PCBD1 and GFRP genes were sequenced. PMID: 24705691

PVS1

Frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 6 leading to nonsense mediated decay

PM2_Supporting

absent from gnomAD

PM3

c.669delC/c.823C>A (p.T278N) in trans (P/LP)

Approved on: 2023-10-13

Published on: 2023-10-13

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