Variant: NM_000277.2(PAH):c.895_897delTTT (p.Phe299del)

CA229837

102886 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: e8c15621-e7e7-4110-bab8-054bbe31fd53

Approved on: 2019-07-14

Published on: 2019-07-15

HGVS expressions

NM_000277.2:c.895_897del
NM_000277.2(PAH):c.895_897delTTT (p.Phe299del)
NC_000012.12:g.102851702_102851704del
CM000674.2:g.102851702_102851704del
NC_000012.11:g.103245480_103245482del
CM000674.1:g.103245480_103245482del
NC_000012.10:g.101769610_101769612del
NG_008690.1:g.70899_70901del
NG_008690.2:g.111707_111709del
NM_000277.1:c.895_897del
NM_001354304.1:c.895_897del
NM_000277.3:c.895_897del
ENST00000307000.7:c.880_882del
ENST00000549247.6:n.654_656del
ENST00000551114.2:n.557_559del
ENST00000553106.5:c.895_897del
ENST00000635477.1:n.56_58del

Uncertain Significance

• Met criteria codes: PP4 PM4 PM2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.895_897del (p.Phe299del) variant in PAH has been reported in 1 individual with PKU without genotype information (BH4 deficiency not ruled out) (PMID: 10541324) . This variant is absent in gnomAD and the ESP population databases. The c.895_897del variant results in an in-frame deletion of phenylalanine 299 in a hydrophobic pocket of the hydroxylase domain of PAH. In summary, this variant meets the criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM4.

Met criteria codes

• PP4: Report one PKU patient with this mutation (table 1), however genotype is not reported. BH4 deficiency is not ruled out.
• PM4: Deletion of codon/amino acid 299
• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline