The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

CA16020866

619148 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: b2e85334-2419-4c6d-a58e-3cf6e83e25c9

HGVS expressions

NM_000277.1:c.817T>C
NC_000012.12:g.102852840A>G
CM000674.2:g.102852840A>G
NC_000012.11:g.103246618A>G
CM000674.1:g.103246618A>G
NC_000012.10:g.101770748A>G
NG_008690.1:g.69763T>C
NG_008690.2:g.110571T>C
NM_000277.2:c.817T>C
NM_001354304.1:c.817T>C
NM_000277.3:c.817T>C
ENST00000307000.7:c.802T>C
ENST00000549247.6:n.576T>C
ENST00000553106.5:c.817T>C

Uncertain Significance

Met criteria codes 3
PP3 PM2 PP4_Moderate
Not Met criteria codes 1
PM3

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The c.817T>C (p.Ser273Pro) variant in PAH has been reported in a Japanese patient with classic PKU. (Biopterin deficiency excluded. PMID: 1114275, PP4_Moderate) It was detected with c.442-2G>A (not in ClinVar). This variant is absent from ExAC, gnomAD, 1000G and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.976. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.
Met criteria codes
PP3
Deleterious effect predicted in SIFT, Polyphen2, MutationTaster. REVEL=0.976
PM2
Absent from ExAC, gnomAD, 1000G, ESP
PP4_Moderate
S273P seen in a Japanese patient with classic PKU (Phe level 36.8 mg/dl). biopterin deficiency excluded. PMID: 11142755

Not Met criteria codes
PM3
Detected with c.442-2G>A, not reported in ClinVar

Approved on: 2018-12-10
Published on: 2019-04-06
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