Variant: NM_000277.3(PAH):c.1038del (p.Leu347fs)

CA229295

102487 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: 9ecda5f7-ae61-4301-84b1-f07b41fa9c9b

Approved on: 2021-10-10

Published on: 2021-12-10

HGVS expressions

NM_000277.3:c.1038del
NM_000277.3(PAH):c.1038del (p.Leu347fs)
NC_000012.12:g.102844365del
CM000674.2:g.102844365del
NC_000012.11:g.103238143del
CM000674.1:g.103238143del
NC_000012.10:g.101762273del
NG_008690.1:g.78240del
NG_008690.2:g.119048del
ENST00000553106.6:c.1038del
ENST00000307000.7:c.1023del
ENST00000549247.6:n.797del
ENST00000551114.2:n.700del
ENST00000553106.5:c.1038del
ENST00000635477.1:n.142del
ENST00000635528.1:n.553del
NM_000277.1:c.1038del
NM_000277.2:c.1038del
NM_001354304.1:c.1038del
NM_001354304.2:c.1038del

Pathogenic

• Met criteria codes: PP4 PM2 PVS1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1038del (p.Leu347fs) variant in PAH has been reported in a Danish PKU patient, serum Phe >600 umol/L; BH4 deficiency excluded (PMID: 8406445; PP4). This frameshift variant is predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 10 out of 13 coding exons (10 out of total exons) (PVS1). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

Met criteria codes

• PP4: PMID: 8406445 - L347fs detected in a Danish PKU patient, serum Phe >600 umol/L; Other causes of hyperphenylalaninemia ruled out (Guttler, 1980)
• PM2: Variant absent from population databases.
• PVS1: Frameshift variant, predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 10 out of 13 coding exons (10 out of total exons).