Variant: NM_001354304.2:c.1002C>A

CA16020918

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: fb06e777-733e-455e-9098-0d6b68c0bea4

Approved on: 2023-10-15

Published on: 2023-10-15

HGVS expressions

NM_001354304.2:c.1002C>A
NC_000012.12:g.102844399G>T
CM000674.2:g.102844399G>T
NC_000012.11:g.103238177G>T
CM000674.1:g.103238177G>T
NC_000012.10:g.101762307G>T
NG_008690.1:g.78204C>A
NG_008690.2:g.119012C>A
ENST00000553106.6:c.1002C>A
ENST00000307000.7:c.987C>A
ENST00000549247.6:n.761C>A
ENST00000551114.2:n.664C>A
ENST00000553106.5:c.1002C>A
ENST00000635477.1:c.106C>A
ENST00000635528.1:n.517C>A
NM_000277.1:c.1002C>A
NM_000277.2:c.1002C>A
NM_001354304.1:c.1002C>A
NM_000277.3:c.1002C>A

Pathogenic

• Met criteria codes: PP4 PVS1 PM2_Supporting

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1002C>A (p.Cys334Ter) variant in PAH is a nonsense variant in exon 10 of 13 predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). It was reported in a PKU patient from Shaanxi with blood Phe concentration over 2.0 mg/dL (PMID: 24510568; PP4). This variant is absent from gnomAD. In summary, this variant meets the criteria to be classified as pathogenic for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH VCEP: PVS1, PM2_supporting, PP4.

Met criteria codes

• PP4: Reported in a PKU patient from Shaanxi; blood Phe concentration was over 2.0 mg/dL. Unknown if BH4 deficiency ruled out (article in Chinese). PMID: 24510568
• PVS1: Nonsense variant in exon 10 of 13. NMD predicted.
• PM2_Supporting: Absent from gnomAD