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Please note this is a beta version of the ClinGen Evidence Repository. This resource is intended to provide access to variant level evidence used and applied by ClinGen Variant Curation Expert Panels in the classification of variants. In this beta version, the evidence is limited to curation notes and referenced literature (PMIDs).

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

CA229570

102693 (ClinVar)

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

HGVS expressions

NM_000277.2:c.472C>T
NM_000277.1:c.472C>T (p.Arg158Trp)
NM_001354304.1:c.472C>T (p.Arg158Trp)
NM_000277.3:c.472C>T
ENST00000307000.7:c.457C>T (p.Arg153Trp)
ENST00000549111.5:n.568C>T
ENST00000551988.5:n.530+10829C>T
ENST00000553106.5:c.472C>T (p.Arg158Trp)
NC_000012.12:g.102866633G>A
CM000674.2:g.102866633G>A
NC_000012.11:g.103260411G>A
CM000674.1:g.103260411G>A
NC_000012.10:g.101784541G>A
NG_008690.1:g.55970C>T
NG_008690.2:g.96778C>T

Pathogenic

Met criteria codes 5
PP4_Moderate PM3_Strong PS3 PP3 PM2

Expert Panel

Evidence Links 5

Evidence submitted by expert panel
PAH VCEP
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
PP4_Moderate
Detected in at least 3 patients with PAH deficiency. BH4 deficiency ruled out in 1 patient.

PM3_Strong
Detected with 3 pathogenic/likely pathogenic variants

PS3
2% mutant enzyme activity in BioPKU
PP3
Predicted deleterious in SIFT, Polyphen-2, MutationTaster. REVEL=0.939
PM2
Extremely low frequency. ExAC MAF=0.00019.
Approved on: 2018-08-10
Published on: 2019-04-06
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