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NM_000277.2(PAH):c.472C>T (p.Arg158Trp)


102693 (ClinVar)

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

HGVS expressions

NM_000277.1:c.472C>T (p.Arg158Trp)
XM_011538422.1:c.472C>T (p.Arg158Trp)
NM_001354304.1:c.472C>T (p.Arg158Trp)
XM_017019370.2:c.472C>T (p.Arg158Trp)
ENST00000307000.7:c.457C>T (p.Arg153Trp)
ENST00000553106.5:c.472C>T (p.Arg158Trp)


Met criteria codes 5
PP3 PM2 PS3 PP4_Moderate PM3_Strong

Expert Panel

Evidence Links 5

Evidence submitted by expert panel
PAH-specific ACMG/AMP criteria applied: PM2: Extremely low frequency. ExAC MAF=0.00019.; PP3: Predicted deleterious in SIFT, Polyphen-2, MutationTaster. REVEL=0.939; PS3: 2% mutant enzyme activity in BioPKU; PP4_Moderate: Detected in at least 3 patients with PAH deficiency. BH4 deficiency ruled out in 1 patient. (PMID:1307609; PMID:10429004; PMID:9634518); PM3_Strong: Detected with 3 pathogenic/likely pathogenic variants (PMID:14681498; PMID:23430918). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PS3, PP4_Moderate, PM3_Strong).
Met criteria codes
Predicted deleterious in SIFT, Polyphen-2, MutationTaster. REVEL=0.939
Extremely low frequency. ExAC MAF=0.00019.
2% mutant enzyme activity in BioPKU
Detected in at least 3 patients with PAH deficiency. BH4 deficiency ruled out in 1 patient.

Detected with 3 pathogenic/likely pathogenic variants

Approved on: 2018-08-10
Published on: 2018-10-02
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