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CA16020930

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 6ccddbbe-2be0-480b-a811-719357485865

HGVS expressions

NM_000277.3:c.1066-1G>T
NC_000012.12:g.102843780C>A
CM000674.2:g.102843780C>A
NC_000012.11:g.103237558C>A
CM000674.1:g.103237558C>A
NC_000012.10:g.101761688C>A
NG_008690.1:g.78823G>T
NG_008690.2:g.119631G>T
NM_000277.1:c.1066-1G>T
NM_000277.2:c.1066-1G>T
NM_001354304.1:c.1066-1G>T
ENST00000307000.7:c.1051-1G>T
ENST00000549247.6:n.825-1G>T
ENST00000551114.2:n.728-1G>T
ENST00000553106.5:c.1066-1G>T
ENST00000635477.1:n.170-1G>T
ENST00000635528.1:n.581-1G>T

Pathogenic

Met criteria codes 3
PM2 PVS1 PP4_Moderate

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
This c.1066-1G>T (IVS10-1G>T) variant in PAH was reported in one Chinese patient with PAH deficiency (PMID: 26503515). DHPR activity, biopterin and/or pteridine analysis was performed to rule out other causes of hyperphenylalaninemia. This variant is absent from the population databases ExAC and gnomAD. This variant in the -1 splice acceptor site results in exon skipping. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4_moderate.
Met criteria codes
PM2
Absent from population databases gnomAD and ExAC.
PVS1
This variant in the -1 splice acceptor site results in exon skipping. The variant disrupts the reading frame and is predicted to undergo nonsense mediated decay (NMD). This variant breaks the splice site according to HSF HSF (-35.29% variation) and MaxEnt (-271.52% variation)
PP4_Moderate
This variant was documented once in a Southern Chinese patient diagnosed with PAH deficiency (PMID: 26503515).

Approved on: 2019-10-18
Published on: 2019-10-18
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