rs368900406
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The NM_002437.5(MPV17):c.376-9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_002437.5 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPV17 | NM_002437.5 | c.376-9T>G | intron_variant | Intron 5 of 7 | ENST00000380044.6 | NP_002428.1 | ||
MPV17 | XM_005264326.5 | c.376-9T>G | intron_variant | Intron 5 of 7 | XP_005264383.1 | |||
MPV17 | XM_017004151.2 | c.328-9T>G | intron_variant | Intron 5 of 7 | XP_016859640.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461710Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21AN XY: 727168
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74350
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease, axonal, type 2EE Pathogenic:5
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not provided Pathogenic:1Uncertain:1
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This sequence change falls in intron 5 of the MPV17 gene. It does not directly change the encoded amino acid sequence of the MPV17 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs368900406, gnomAD 0.003%). This variant has been observed in individual(s) with peripheral sensorimotor neuropathy (PMID: 30298599). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 593343). Studies have shown that this variant results in skipping of exon 6, but is expected to preserve the integrity of the reading-frame (PMID: 30298599). For these reasons, this variant has been classified as Pathogenic. -
MPV17-related mitochondrial DNA maintenance defect Pathogenic:1
RNA sequencing showed change in splicing -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at