Evidence Repository
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 CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

Variant: NM_000277.3(PAH):c.226G>T (p.Glu76Ter)

CA16020752

495789 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 848a19e1-be21-4d94-b0f8-1c6fd86f2e1b
Approved on: 2023-10-15
Published on: 2023-10-15

HGVS expressions

NM_000277.3:c.226G>T
NM_000277.3(PAH):c.226G>T (p.Glu76Ter)
NC_000012.12:g.102894861C>A
CM000674.2:g.102894861C>A
NC_000012.11:g.103288639C>A
CM000674.1:g.103288639C>A
NC_000012.10:g.101812769C>A
NG_008690.1:g.27742G>T
NG_008690.2:g.68550G>T
ENST00000553106.6:c.226G>T
ENST00000307000.7:c.211G>T
ENST00000546844.1:c.226G>T
ENST00000548677.2:n.313G>T
ENST00000548928.1:n.148G>T
ENST00000549111.5:n.322G>T
ENST00000550978.6:c.210G>T
ENST00000551337.5:c.226G>T
ENST00000551988.5:n.315G>T
ENST00000553106.5:c.226G>T
NM_000277.1:c.226G>T
NM_000277.2:c.226G>T
NM_001354304.1:c.226G>T
NM_001354304.2:c.226G>T
More

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PP4
Not Met criteria codes 1
BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The NM_000277.3(PAH):c.226G>T (p.Glu76Ter) is a nonsense variant in exon 3/13 of PAH, and is predicted to result in PTC with removal of >10% of the protein and NMD (PVS1). The variant is absent from population databases, including gnomAD, ExAC, 1000 Genomes, or ESP (PM2_supporting). The variant has been previously reported in a patient with classic PKU (plasma Phe >1200 uM) (PMID: 17096675) with BH4 deficiency not noted to have been formally excluded (PP4), in cis with the c.1089delG variant (ClinVar Pathogenic, see ID 102518). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2_supporting, PP4.
Met criteria codes
PM2_Supporting
The variant is absent from population databases, including gnomAD, ExAC, 1000 Genomes, or ESP (PM2).
PVS1
nonsense variant in exon 3/13 of PAH, , and is predicted to result in PTC with removal of >10% of the protein and NMD (PVS1).
PP4
Complex allele p.E76X* + c.1089delG has been previously reported in a patient with classic PKU (plasma Phe >1200 uM) (PMID: 17096675) with BH4 deficiency not noted to have been formally excluded (PP4)
Not Met criteria codes
BP2
The variant has been previously reported in a patient with classic PKU (plasma Phe >1200 uM) (PMID: 17096675) with BH4 deficiency not noted to have been formally excluded (PP4), in cis with the c.1089delG variant (ClinVar Pathogenic, see ID 102518) and no further details regarding the patient’s genotype appear to be included
Curation History
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.
¤ Powered by BCM's Genboree.