rs1555209575
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PP4PVS1PM2
This summary comes from the ClinGen Evidence Repository: The c.127G>T (p.Glu43*) variant is a nonsense variant in exon 2 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function. It has been reported in 2 individuals with PKU (BH4 deficiency not excluded). (PP4; PMID:26503515). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA16020729/MONDO:0009861/006
Frequency
Consequence
NM_000277.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.127G>T | p.Glu43Ter | stop_gained | 2/13 | ENST00000553106.6 | |
PAH | NM_001354304.2 | c.127G>T | p.Glu43Ter | stop_gained | 3/14 | ||
PAH | XM_017019370.2 | c.127G>T | p.Glu43Ter | stop_gained | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.127G>T | p.Glu43Ter | stop_gained | 2/13 | 1 | NM_000277.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Pathogenic:2
Pathogenic, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Apr 03, 2019 | The c.127G>T (p.Glu43*) variant is a nonsense variant in exon 2 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function. It has been reported in 2 individuals with PKU (BH4 deficiency not excluded). (PP4; PMID: 26503515). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 08, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at