Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.3(PAH):c.443_509+1del

CA229552

102681 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1bf52a23-a03e-4000-871d-889b26af8ff3

HGVS expressions

NM_000277.3:c.443_509+1del

NM_000277.3(PAH):c.443_509+1del

NC_000012.12:g.102866596_102866663del

CM000674.2:g.102866596_102866663del

NC_000012.11:g.103260374_103260441del

CM000674.1:g.103260374_103260441del

NC_000012.10:g.101784504_101784571del

NG_008690.1:g.55941_56008del

NG_008690.2:g.96749_96816del

ENST00000553106.6:c.443_509+1del

ENST00000307000.7:c.428_494+1del

ENST00000549111.5:n.539_605+1del

ENST00000551988.5:n.530+10800_530+10867del

ENST00000553106.5:c.443_509+1del

NM_000277.1:c.443_509+1del

NM_000277.2:c.443_509+1del

NM_001354304.1:c.443_509+1del

NM_001354304.2:c.443_509+1del

Pathogenic

PVS1 PM2 PP4_Moderate

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.443_509+1del (p.Ex5del) variant in PAH is a deletion of exon 5 and is predicted to lead to a frameshift at His170, premature protein truncation, and NMD (PVS1). It is absent from ethnically diverse control databases, including gnomAD (structural variant version, gnomAD SVs v2.1) (PM2). It has been previously reported in one patient with PKU (BH4 deficiency excluded by sequencing of the genes in the BH4 cofactor metabolism pathway) (PP4_Moderate) (PMID: 23942198) in presumed trans with the p.G332R variant (unclassified/VUS). It is also noted in ClinVar (ID 102681) without a classification. Classification: Pathogenic Supporting Criteria: PVS1; PM2; PP4_Moderate

PVS1

The c.443_509+1del (p.Ex5del) variant in PAH is a deletion of exon 5 and is predicted to lead to a frameshift at His170, premature protein truncation, and NMD (PVS1).

PM2

It is absent from ethnically diverse control databases, including gnomAD (structural variant version, gnomAD SVs v2.1) (PM2).

PP4_Moderate

It has been previously reported in one patient with PKU (BH4 deficiency excluded by sequencing of the genes in the BH4 cofactor metabolism pathway) (PP4_Moderate) (PMID: 23942198) in presumed trans with the p.G332R variant (unclassified/VUS).

Approved on: 2020-05-22

Published on: 2021-03-21

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.