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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.3(PAH):c.1007A>G (p.Gln336Arg)

CA229266

102466 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4fe66161-cce0-4b02-9d1c-124f868365a9

HGVS expressions

NM_000277.3:c.1007A>G

NM_000277.3(PAH):c.1007A>G (p.Gln336Arg)

ENST00000553106.6:c.1007A>G

ENST00000307000.7:c.992A>G

ENST00000549247.6:n.766A>G

ENST00000551114.2:n.669A>G

ENST00000553106.5:c.1007A>G

ENST00000635477.1:n.111A>G

ENST00000635528.1:n.522A>G

NM_000277.1:c.1007A>G

NM_000277.2:c.1007A>G

NM_001354304.1:c.1007A>G

NM_001354304.2:c.1007A>G

NC_000012.12:g.102844394T>C

CM000674.2:g.102844394T>C

NC_000012.11:g.103238172T>C

CM000674.1:g.103238172T>C

NC_000012.10:g.101762302T>C

NG_008690.1:g.78209A>G

NG_008690.2:g.119017A>G

Uncertain Significance

PM3_Supporting PP4 PP3 PM2

PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1007A>G (p.Gln336Arg) variant in PAH has been reported in a Chinese patient with classical PKU, BH4 deficiency not assessed. It was detected with pathogenic variant p.R243Q, parental analysis not reported (PMID: 16256386). This variant is absent from controls in ExAC, gnomAD, 1000 Genomes, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.958. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4, PM3_supporting.

PM3_Supporting

Detected with R243Q, parental analysis not reported PMID: 16256386

PP4

Reported in a patient with classical PKU, BH4 deficiency not assessed. PMID: 16256386

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster. REVEL=0.958

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, ESP

PM5

No other missense changes at this aa

Approved on: 2019-12-15

Published on: 2021-05-14

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