Evidence Repository - Clinical Genome Resources

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

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Variant: NM_000277.2(PAH):c.811C>T (p.His271Tyr)

CA229784

102849 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 45244248-8a0a-4565-9536-b465ac28a4ee

HGVS expressions

NM_000277.2:c.811C>T

NM_000277.2(PAH):c.811C>T (p.His271Tyr)

NC_000012.12:g.102852846G>A

CM000674.2:g.102852846G>A

NC_000012.11:g.103246624G>A

CM000674.1:g.103246624G>A

NC_000012.10:g.101770754G>A

NG_008690.1:g.69757C>T

NG_008690.2:g.110565C>T

NM_000277.1:c.811C>T

NM_001354304.1:c.811C>T

NM_000277.3:c.811C>T

ENST00000307000.7:c.796C>T

ENST00000549247.6:n.570C>T

ENST00000553106.5:c.811C>T

Uncertain Significance

PM2 PP3 PP4

PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.811C>T (p.His271Tyr) variant in PAH has been reported in 2 unrelated PKU patients. BH4 deficiencies not assessed. (PMID: 9012412) A deleterious effect is predicted in SIFT, Polyphen2, MutationTaster, and REVEL=0.978. This variant has an extremely low frequency in ExAC, 1000G, ESP, and gnomAD (MAF=0.00001). . In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4.

PM2

Extremely low frequency in ExAC, 1000G, ESP (MAF=0.00001)

PP3

Deleterious effect predicted in SIFT, Polyphen2, MutationTaster. REVEL=0.978

PP4

H271Y was seen in 2 unrelated PKU patients. BH4 deficiencies not assessed. PMID: 9012412.

PKU patients from four centers in three countries of Great Britain were studied. H271Y was seen in 2 unrelated patients. PubMed:9012412

PM5

H271L Likely pathogenic in ClinVar

Approved on: 2018-12-10

Published on: 2019-04-06

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