NM_001354304.2:c.912+1G>T

CA16020895

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: 1a7c9b7f-8802-43dd-9eee-ba0292eefa85

Approved on: 2020-07-24

Published on: 2020-07-24

HGVS expressions

NM_001354304.2:c.912+1G>T
NM_000277.1:c.912+1G>T
NM_000277.2:c.912+1G>T
NM_001354304.1:c.912+1G>T
NM_000277.3:c.912+1G>T
ENST00000307000.7:c.897+1G>T
ENST00000549247.6:n.671+1G>T
ENST00000551114.2:n.574+1G>T
ENST00000553106.5:c.912+1G>T
ENST00000635477.1:n.73+1G>T
NC_000012.12:g.102851686C>A
CM000674.2:g.102851686C>A
NC_000012.11:g.103245464C>A
CM000674.1:g.103245464C>A
NC_000012.10:g.101769594C>A
NG_008690.1:g.70917G>T
NG_008690.2:g.111725G>T

Pathogenic

• Met criteria codes: PVS1 PP4 PM2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.912+1G>T variant is a canonical splice donor in PAH in which exon skipping disrupts the reading frame and is predicted to undergo nonsense mediated-decay. This variant was identified in 1 patient with PAH deficiency in a Catalonian cohort (PMID 10598814). This variant is absent from population databases. In summary, c.912+1G>T in PAH meets criteria to be classified as pathogenic. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, and PP4.

Met criteria codes

• PVS1: This variant is in the +1 donor site of IVS8. This results in exon skipping that disrupts reading frame. Predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Altered region is critical to protein function. Number of pathogenic non-nonsense variants in skipped exon: 28. Variant removes more than 10% of transcript (5.2% of transcript.)
• PP4: This variant was identified in 1 patient with Non-PKU HPA in Catalonia cohort PMID 10598814
• PM2: This variant is absent from databases such as 1000G, ESP, and gnomAD.