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.338_341del

CA16020767

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1bfa5cfc-632e-498e-8798-41bf36bbd475

HGVS expressions

NM_001354304.2:c.338_341del

NC_000012.12:g.102894747_102894750del

CM000674.2:g.102894747_102894750del

NC_000012.11:g.103288525_103288528del

CM000674.1:g.103288525_103288528del

NC_000012.10:g.101812655_101812658del

NG_008690.1:g.27854_27857del

NG_008690.2:g.68662_68665del

ENST00000553106.6:c.338_341del

ENST00000307000.7:c.323_326del

ENST00000546844.1:c.338_341del

ENST00000548928.1:n.260_263del

ENST00000549111.5:n.434_437del

ENST00000550978.6:c.322_325del

ENST00000551337.5:c.338_341del

ENST00000551988.5:n.427_430del

ENST00000553106.5:c.338_341del

NM_000277.1:c.338_341del

NM_000277.2:c.338_341del

NM_001354304.1:c.338_341del

NM_000277.3:c.338_341del

Pathogenic

PVS1 PM2_Supporting PP4_Moderate

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.338_341del (p.Lys113ArgfsTer81) variant in PAH is a frameshift predicted to cause a premature stop codon in exon 3 leading to nonsense mediated decay exon. It was reported in a Japanese PKU patient with BH4 deficiency ruled out (PMID: 21307867). 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, PM2_supporting.

PVS1

Frameshift variant in exon 3 with NMD predicted

PM2_Supporting

absent from gnomAD

PP4_Moderate

Reported in a Japanese patient with PKU (serum phenylalanine level higher than 0.18mM; analysis of dihydropteridine reductase activity in red blood cells, biopterin loading test and/or pteridine analysis in urine. PMID: 21307867

PM3

genotype not reported

Approved on: 2023-10-13

Published on: 2023-10-13

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