NM_000310.4:c.871C>T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000310.4(PPT1):c.871C>T(p.Gln291*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q291Q) has been classified as Likely benign.
Frequency
Consequence
NM_000310.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPT1 | NM_000310.4 | c.871C>T | p.Gln291* | stop_gained | Exon 9 of 9 | ENST00000642050.2 | NP_000301.1 | |
PPT1 | NM_001363695.2 | c.799C>T | p.Gln267* | stop_gained | Exon 8 of 8 | NP_001350624.1 | ||
PPT1 | NM_001142604.2 | c.562C>T | p.Gln188* | stop_gained | Exon 6 of 6 | NP_001136076.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 1 Pathogenic:2
Variant summary: PPT1 c.871C>T (p.Gln291X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position (p.W296X) has been reported in a patient (PMID: 9664077). The variant was absent in 251410 control chromosomes (gnomAD). c.871C>T has been reported in the literature in a compound heterozygote individual affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease), who had another truncating variant in trans (Waliany 2000). This patient had undetectable enzyme activity, and disease specific electronmicroscopic findings (Waliany 2000). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at