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

Variant: NM_000277.2(PAH):c.535T>A (p.Tyr179Asn)

CA229613

102729 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 1530f57a-9096-4f98-a934-15ce8f576c73

HGVS expressions

NM_000277.2:c.535T>A
NM_000277.2(PAH):c.535T>A (p.Tyr179Asn)
NC_000012.12:g.102855307A>T
CM000674.2:g.102855307A>T
NC_000012.11:g.103249085A>T
CM000674.1:g.103249085A>T
NC_000012.10:g.101773215A>T
NG_008690.1:g.67296T>A
NG_008690.2:g.108104T>A
NM_000277.1:c.535T>A
NM_001354304.1:c.535T>A
NM_000277.3:c.535T>A
ENST00000307000.7:c.520T>A
ENST00000549111.5:n.631T>A
ENST00000551988.5:n.556T>A
ENST00000553106.5:c.535T>A

Likely Pathogenic

Met criteria codes 4
PM3 PM2 PP4_Moderate PP3

Evidence Links 1

Evidence submitted by expert panel
Phenylketonuria VCEP
PAH-specific ACMG/AMP criteria applied: PM2: Absent from ExAC, gnomAD, 1000G, ESP; PP3: Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.929; PP4_Moderate: Detected in 1 PKU patient, primary BH4 deficiency excluded. Upgraded per ClinGen PAH EP. (PMID:23430918); PM3: Detected with c.1066-11G>A (P) (PMID:23430918). 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, PP4_Moderate, PM3).
Met criteria codes
PM3
Detected with c.1066-11G>A (P)

PM2
Absent from ExAC, gnomAD, 1000G, ESP
PP4_Moderate
Detected in 1 PKU patient, primary BH4 deficiency excluded. Upgraded per ClinGen PAH EP.

PP3
Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.929
Approved on: 2018-08-10
Published on: 2019-08-17
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