rs1553383467

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_002437.5(MPV17):​c.297T>A​(p.Cys99*) 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

MPV17
NM_002437.5 stop_gained

Scores

2
4
1

Clinical Significance

Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 0.758
Variant links:
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 18 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 2-27312572-A-T is Pathogenic according to our data. Variant chr2-27312572-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 522373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MPV17NM_002437.5 linkc.297T>A p.Cys99* stop_gained 5/8 ENST00000380044.6 NP_002428.1 P39210A0A0S2Z3Z9
MPV17XM_005264326.5 linkc.297T>A p.Cys99* stop_gained 5/8 XP_005264383.1 P39210A0A0S2Z3Z9
MPV17XM_017004151.2 linkc.249T>A p.Cys83* stop_gained 5/8 XP_016859640.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MPV17ENST00000380044.6 linkc.297T>A p.Cys99* stop_gained 5/81 NM_002437.5 ENSP00000369383.1 P39210

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Pathogenic:2
Likely pathogenic, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineDec 01, 2017- -
Likely pathogenic, criteria provided, single submittercurationSIB Swiss Institute of BioinformaticsAug 13, 2019This variant is interpreted as a Likely pathogenic for Mitochondrial DNA depletion syndrome 6, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PVS1-strong. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
35
DANN
Uncertain
0.99
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.97
D
Vest4
0.87
ClinPred
0.98
D
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553383467; hg19: chr2-27535439; API