Variant: NM_000277.3(PAH):c.452A>G (p.Asp151Gly)

CA229554

102683 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: 3f8cd12f-4f9e-4eb7-b464-64d5b77c6e35

Approved on: 2024-11-17

Published on: 2024-11-17

HGVS expressions

NM_000277.3:c.452A>G
NM_000277.3(PAH):c.452A>G (p.Asp151Gly)
NC_000012.12:g.102866653T>C
CM000674.2:g.102866653T>C
NC_000012.11:g.103260431T>C
CM000674.1:g.103260431T>C
NC_000012.10:g.101784561T>C
NG_008690.1:g.55950A>G
NG_008690.2:g.96758A>G
ENST00000553106.6:c.452A>G
ENST00000307000.7:c.437A>G
ENST00000549111.5:n.548A>G
ENST00000551988.5:n.530+10809A>G
ENST00000553106.5:c.452A>G
NM_000277.1:c.452A>G
NM_000277.2:c.452A>G
NM_001354304.1:c.452A>G
NM_001354304.2:c.452A>G

Likely Pathogenic

• Met criteria codes: PP3_Strong PP4 PM2_Supporting

• Not Met criteria codes: PM5

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specification: ClinGen Phenylketonuria Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PAH Version 2.0.0

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.452A>G (p.Asp151Gly) variant in PAH is reported in a Spanish patient with phenylketonuria (PMID: 8981952); the second allele/genotype was not reported. It is absent from gnomAD. Multiple lines of computational evidence support a deleterious effect (REVEL=0.98). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2_supporting, PP3_strong, PP4.

Met criteria codes

• PP3_Strong: Predicted deleterious in REVEL=0.98, SIFT, PP-2, MutationTaster
• PP4: Reported in a Spanish patient with PKU (serum phenylalanine levels at diagnosis were >600 umol/liter and after exclusion of a defect in tetrahydrobiopterine metabolism) PMID: 8981952
• PM2_Supporting: Absent from gnomAD v4.1.0

Not Met criteria codes

• PM5: D151H has no interpretation in ClinVar