The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document


Variant: NM_000277.1:c.510-19_667del

CA16020833

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 7a382923-29c1-41c1-a7b6-c331affb9e93

HGVS expressions

NM_000277.1:c.510-19_667del
NC_000012.12:g.102855177_102855353del
CM000674.2:g.102855177_102855353del
NC_000012.11:g.103248955_103249131del
CM000674.1:g.103248955_103249131del
NC_000012.10:g.101773085_101773261del
NG_008690.1:g.67252_67428del
NG_008690.2:g.108060_108236del
ENST00000553106.6:c.510-19_667del
ENST00000307000.7:c.495-19_652del
ENST00000549111.5:n.606-19_763del
ENST00000553106.5:c.510-19_667del
NM_000277.2:c.510-19_667del
NM_001354304.1:c.510-19_667del
NM_000277.3:c.510-19_667del
NM_001354304.2:c.510-19_667del

Pathogenic

Met criteria codes 4
PM3_Supporting PP4 PVS1 PM2_Supporting

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PAH Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The c.510-19_667del variant in PAH involves part of exon 6, predicted to result in frameshift and NMD (PVS1). It has been reported in 1 individual with PKU. (PP4; PMID: 23842451). This variant is absent from gnomAD (PM2_supporting). This variant was detected with p.G272* (Pathogenic in ClinVar; PM3). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2_supporting, PM3_supporting, PP4.
Met criteria codes
PM3_Supporting
Detected with G272*, Pathogenic in ClinVar. Parental confirmation not reported.

PP4
c.510-21_665del was detected in one patient with Phe level 855. BH4 deficiency not reported/assessed. PMID: 23842451

PVS1
Partial exon deletion: His170, c.665 is codon 222 (Asp) HSF: Alteration of the WT acceptor site, most probably affecting splicing. MaxENT: 280-700% variation. Overlap with coding exons and predicted to undergo NMD: results in frameshift, percentage of exonic region overlapped: 11.63% (158/1359)
PM2_Supporting
Absent from ExAC, gnomAD, 1000G, ESP
Approved on: 2023-12-30
Published on: 2023-12-30
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