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]

Variant: NM_000277.2(PAH):c.1033G>A (p.Ala345Thr)

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Curation History
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CA229291

102483 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e8f41b26-818c-4003-b73f-0be5c4dcd234

Approved on: 2018-08-10

Published on: 2019-08-17

HGVS expressions

NM_000277.2:c.1033G>A

NM_000277.2(PAH):c.1033G>A (p.Ala345Thr)

NC_000012.12:g.102844368C>T

CM000674.2:g.102844368C>T

NC_000012.11:g.103238146C>T

CM000674.1:g.103238146C>T

NC_000012.10:g.101762276C>T

NG_008690.1:g.78235G>A

NG_008690.2:g.119043G>A

NM_000277.1:c.1033G>A

NM_001354304.1:c.1033G>A

NM_000277.3:c.1033G>A

ENST00000307000.7:c.1018G>A

ENST00000549247.6:n.792G>A

ENST00000551114.2:n.695G>A

ENST00000553106.5:c.1033G>A

ENST00000635477.1:n.137G>A

ENST00000635528.1:n.548G>A

Likely Pathogenic

PP3 PM5 PM3 PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PM2: Absent from controls in ExaC, 100 Genomes, ESP, and gnomAD; PP3: Deleterious effected predicted by SIFT, Polyphen2, and MutationTaster; PM5: A345S (Variant ID 102484) predicted pathogenic in ClinVar; PP4_Moderate: Found in two individuals with Classic PKU on exon 10.Urinary pterin analysis and dihydropteridine reductase (DHPR) assay were performed t (PMID:15503242); PM3: Found in trans with R243Q (pathogenic in ClinVar). (PMID:15503242). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PM5, PP4_Moderate, PM3).

PP3

Deleterious effected predicted by SIFT, Polyphen2, and MutationTaster

PM5

A345S (Variant ID 102484) predicted pathogenic in ClinVar

PM3

Found in trans with R243Q (pathogenic in ClinVar).

Found in trans with R243Q (pathogenic in ClinVar) in Patients 53 and 65, and G332V (not in ClinVar). PubMed:15503242

PM2

Absent from controls in ExaC, 100 Genomes, ESP, and gnomAD

PP4_Moderate

Found in two individuals with Classic PKU on exon 10.Urinary pterin analysis and dihydropteridine reductase (DHPR) assay were performed t

Found in two individuals with Classic PKU on exon 10. Found in trans with G332V in a individual with classic PKU. Found in trans with R243Q in two individuals, one with Classic PKU and one NA. Urinary pterin analysis and dihydropteridine reductase (DHPR) assay were performed t PubMed:15503242

Curation History

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