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


102729 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance

HGVS expressions

NM_000277.1:c.535T>A (p.Tyr179Asn)
NM_001354304.1:c.535T>A (p.Tyr179Asn)
ENST00000307000.7:c.520T>A (p.Tyr174Asn)
ENST00000553106.5:c.535T>A (p.Tyr179Asn)

Likely Pathogenic

Met criteria codes 4
PP4_Moderate PP3 PM3 PM2

Expert Panel

Evidence Links 1

Evidence submitted by expert panel
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
Detected in 1 PKU patient, primary BH4 deficiency excluded. Upgraded per ClinGen PAH EP.

Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.929
Detected with c.1066-11G>A (P)

Absent from ExAC, gnomAD, 1000G, ESP
Approved on: 2018-08-10
Published on: 2018-12-10
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