rs267606615
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The ENST00000362079.2(MT-CO3):c.173G>A(p.Trp58Ter) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Mitomap GenBank:
Absent
Consequence
MT-CO3
ENST00000362079.2 stop_gained
ENST00000362079.2 stop_gained
Scores
Clinical Significance
MM-w-lactic-acidosis
Conservation
PhyloP100: 5.58
Genes affected
MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.779 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
No frequency data in Mitomap. Probably very rare.
PP5
?
Variant M-9379-G-A is Pathogenic according to our data. Variant chrM-9379-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9657.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX3 | COX3.1 use as main transcript | c.173G>A | p.Trp58Ter | stop_gained | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-CO3 | ENST00000362079.2 | c.173G>A | p.Trp58Ter | stop_gained | 1/1 | P1 |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap
MM-w-lactic-acidosis
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mitochondrial complex IV deficiency, nuclear type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2002 | - - |
Mitochondrial myopathy with reversible cytochrome C oxidase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Oct 17, 2019 | The NC_012920.1:m.9379G>A (YP_003024032.1:p.Trp58Ter) variant in MTCO3 gene is interpretated to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PS6, PM8, PM9, PM10 - |
Mitochondrial disease Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Pathogenic and reported on 04-11-2016 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
MutationTaster
Benign
A
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at