NM_001354304.2:c.970-1G>T

CA16020910

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: 5ba28087-6da9-47fd-ba67-e5370810d5ac

Approved on: 2020-05-18

Published on: 2020-05-18

HGVS expressions

NM_001354304.2:c.970-1G>T
NC_000012.12:g.102844432C>A
CM000674.2:g.102844432C>A
NC_000012.11:g.103238210C>A
CM000674.1:g.103238210C>A
NC_000012.10:g.101762340C>A
NG_008690.1:g.78171G>T
NG_008690.2:g.118979G>T
NM_000277.1:c.970-1G>T
NM_000277.2:c.970-1G>T
NM_001354304.1:c.970-1G>T
NM_000277.3:c.970-1G>T
ENST00000307000.7:c.955-1G>T
ENST00000549247.6:n.729-1G>T
ENST00000551114.2:n.632-1G>T
ENST00000553106.5:c.970-1G>T
ENST00000635477.1:n.74-1G>T
ENST00000635528.1:n.485-1G>T

Likely Pathogenic

• Met criteria codes: PP4 PM2 PVS1_Strong

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.970-1G>T variant in PAH is a canonical splice-site variant predicted to lead to skipping of exon 10 (PVS1_Strong). It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). It has been reported in two probands with classic PKU (as defined by abnormal blood Phe levels) (PMID: 27469133); BH4 deficiency does not appear to have been excluded, and there does not appear to be further genotype-level information (PP4). Classification: Likely Pathogenic Supporting Criteria: PVS1_Strong; PM2; PP4

Met criteria codes

• PP4: It has been reported in two probands with classic PKU (as defined by abnormal blood Phe levels) (PMID: 27469133); BH4 deficiency does not appear to have been excluded, and there does not appear to be further genotype-level information (PP4).
• PM2: It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).
• PVS1_Strong: The c.970-1G>T variant in PAH is a canonical splice-site variant predicted to lead to skipping of exon 10 (PVS1_Strong).