rs267607262
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4
The NM_002437.5(MPV17):c.234_242del(p.Gly79_Thr81del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MPV17
NM_002437.5 inframe_deletion
NM_002437.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.22
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 Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a chain Protein Mpv17 (size 175) in uniprot entity MPV17_HUMAN there are 36 pathogenic changes around while only 6 benign (86%) in NM_002437.5
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_002437.5.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| MPV17 | NM_002437.5 | c.234_242del | p.Gly79_Thr81del | inframe_deletion | 4/8 | ENST00000380044.6 | |
| MPV17 | XM_005264326.5 | c.234_242del | p.Gly79_Thr81del | inframe_deletion | 4/8 | ||
| MPV17 | XM_017004151.2 | c.186_194del | p.Gly63_Thr65del | inframe_deletion | 4/8 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MPV17 | ENST00000380044.6 | c.234_242del | p.Gly79_Thr81del | inframe_deletion | 4/8 | 1 | NM_002437.5 | P1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727248
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GnomAD4 genome
GnomAD4 genome
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Uncertain:1
| Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Aug 13, 2019 | This variant is interpreted as a variant of uncertain significance for Mitochondrial DNA depletion syndrome 6, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PM3. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at