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.1A>G (p.Met1Val)

CA114360

586 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 89f04437-ed5d-4735-8c4a-a9b1d91d10ea

HGVS expressions

NM_000277.2:c.1A>G
NM_000277.2(PAH):c.1A>G (p.Met1Val)
NC_000012.12:g.102917130T>C
CM000674.2:g.102917130T>C
NC_000012.11:g.103310908T>C
CM000674.1:g.103310908T>C
NC_000012.10:g.101835038T>C
NG_008690.1:g.5473A>G
NG_008690.2:g.46281A>G
NM_000277.1:c.1A>G
NM_001354304.1:c.1A>G
NM_000277.3:c.1A>G
ENST00000307000.7:c.-147A>G
ENST00000546844.1:c.1A>G
ENST00000547319.1:n.312A>G
ENST00000549111.5:n.97A>G
ENST00000551337.5:c.1A>G
ENST00000551988.5:n.90A>G
ENST00000553106.5:c.1A>G
ENST00000635500.1:n.29-4232A>G

Pathogenic

Met criteria codes 4
PP4_Moderate PS3 PM2 PM3
Unmet criteria codes 1
PVS1

Expert Panel

Evidence Links 2

Evidence submitted by expert panel
PAH VCEP
PAH-specific ACMG/AMP criteria applied: PM2: gnomAD MAF=0.00002; PP4_Moderate: Seen in PKU patients. BH4 disorders ruled out. (PMID:2574002); PS3: <3% (PMID:9450897). PM3: Detected in trans with known pathogenic variants. 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, PM3, PP4_Moderate, PS3). Updated to reflect new PVS1 recommendations.
Met criteria codes
PP4_Moderate
Seen in PKU patients. BH4 disorders ruled out.

PS3
<3%

PM2
gnomAD MAF=0.00002
PM3
Detected in trans with c.1315+1G>A (known pathogenic), and also in the homozygous state.

Unmet criteria codes
PVS1
Initiation codon variant
Approved on: 2019-03-23
Published on: 2019-05-10
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