rs766160589
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002437.5(MPV17):c.284del(p.Gly95AlafsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MPV17
NM_002437.5 frameshift
NM_002437.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.188
Genes affected
MPV17 (HGNC:7224): (mitochondrial inner membrane protein MPV17) This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-27312584-GC-G is Pathogenic according to our data. Variant chr2-27312584-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 2203028.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-27312584-GC-G is described in Lovd as [Likely_pathogenic]. Variant chr2-27312584-GC-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPV17 | NM_002437.5 | c.284del | p.Gly95AlafsTer7 | frameshift_variant | 5/8 | ENST00000380044.6 | |
MPV17 | XM_005264326.5 | c.284del | p.Gly95AlafsTer7 | frameshift_variant | 5/8 | ||
MPV17 | XM_017004151.2 | c.236del | p.Gly79AlafsTer7 | frameshift_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPV17 | ENST00000380044.6 | c.284del | p.Gly95AlafsTer7 | frameshift_variant | 5/8 | 1 | NM_002437.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461728Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727170
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727170
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 11, 2022 | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 19748572). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly95Alafs*7) in the MPV17 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at