Variant: NM_000277.3(PAH):c.1163_1164del (p.Val388fs)

CA229367

102542 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: e230cc01-bee4-4942-9bba-4fa4aa43f05d

Approved on: 2020-10-29

Published on: 2020-10-29

HGVS expressions

NM_000277.3:c.1163_1164del
NM_000277.3(PAH):c.1163_1164del (p.Val388fs)
NM_000277.1:c.1163_1164del
NM_000277.2:c.1163_1164del
NM_001354304.1:c.1163_1164del
NM_001354304.2:c.1163_1164del
ENST00000307000.7:c.1148_1149del
ENST00000549247.6:n.922_923del
ENST00000551114.2:n.825_826del
ENST00000553106.5:c.1163_1164del
ENST00000635477.1:n.267_268del
ENST00000635528.1:n.678_679del
NC_000012.12:g.102843682_102843683del
CM000674.2:g.102843682_102843683del
NC_000012.11:g.103237460_103237461del
CM000674.1:g.103237460_103237461del
NC_000012.10:g.101761590_101761591del
NG_008690.1:g.78921_78922del
NG_008690.2:g.119729_119730del

Pathogenic

• Met criteria codes: PVS1 PP4 PM2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1163_1164del (p.Val388fs) variant in PAH has been reported in 1 female patient with classic PKU, Phe = 1210umol/L; BH4 deficiency not excluded (PMID: 10200057; PP4). This frameshift variant is predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 11 out of 13 coding exons (11 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

• PVS1: Frameshift variant, predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 11 out of 13 coding exons (11 out of total exons).
• PP4: PMID: 10200057 - V388fs detected in 1 female patient with classic PKU, Phe = 1210umol/L; BH4 deficiency not excluded
• PM2: Variant absent from population databases.