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

Criteria Specification: CSpec Registry PDF

Variant: NM_000277.2(PAH):c.500A>G (p.Asn167Ser)

CA229585

102703 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 33e1f5d5-20ab-45d2-8dcd-4eba431a8642

HGVS expressions

NM_000277.2:c.500A>G

NM_000277.2(PAH):c.500A>G (p.Asn167Ser)

NC_000012.12:g.102866605T>C

CM000674.2:g.102866605T>C

NC_000012.11:g.103260383T>C

CM000674.1:g.103260383T>C

NC_000012.10:g.101784513T>C

NG_008690.1:g.55998A>G

NG_008690.2:g.96806A>G

NM_000277.1:c.500A>G

NM_001354304.1:c.500A>G

NM_000277.3:c.500A>G

ENST00000307000.7:c.485A>G

ENST00000549111.5:n.596A>G

ENST00000551988.5:n.530+10857A>G

ENST00000553106.5:c.500A>G

Uncertain Significance

PP4 BS1

PP3

Expert Panel

Phenylketonuria VCEP

Evidence Links 1

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PP4: N167S was observed in 1 case (genotype N167S/-) with benign persistent hyperphenylalaninemia (200-600 uM). (PMID:11385716); BS1: gnomAD MAF: 0.01461. In summary this variant meets criteria to be classified as uncertain significance for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PP4, BS1).

PP4

N167S was observed in 1 case (genotype N167S/-) with benign persistent hyperphenylalaninemia (200-600 uM).

N167S was observed in 1 case (genotype N167S/-) with benign persistent hyperphenylalaninemia. Benign persistent hyperphenylalaninemia was diagnosed in cases with the untreated PHE level of 4-9.9 mg/dl (200-600 µM). PubMed:11385716

BS1

gnomAD MAF: 0.01461

PP3

Conflicting interpretations of pathogenicity: benign and tolerated in SIFT, PP2. Deleterious in MutationTaster

Approved on: 2018-08-13

Published on: 2019-04-06

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