17-15231073-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000304.4(PMP22):c.327C>A(p.Cys109*) variant causes a stop gained change involving the alteration of a non-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. C109C) has been classified as Benign.
Frequency
Consequence
NM_000304.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMP22 | NM_000304.4 | c.327C>A | p.Cys109* | stop_gained | Exon 5 of 5 | ENST00000312280.9 | NP_000295.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:2
The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. Moderate co-segregation with disease in affected individuals from a single family. -
Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23224996, 15099590, 22131320, 32376792) -
Charcot-Marie-Tooth disease Pathogenic:1
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Charcot-Marie-Tooth disease, type I Pathogenic:1
This sequence change creates a premature translational stop signal (p.Cys109*) in the PMP22 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the PMP22 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neuropathy (PMID: 15099590, 22131320). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217237). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at