M-7628-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Mitomap GenBank:
𝑓 0.0 ( AC: 2 )

Consequence

COX2
missense

Scores

Apogee2
Pathogenic
0.56

Clinical Significance

Uncertain significance criteria provided, single submitter U:1
No linked disesase in Mitomap

Conservation

PhyloP100: 4.77
Variant links:
Genes affected
COX2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]
TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))
COX1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]
TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COX2unassigned_transcript_4802 c.43C>A p.Pro15Thr missense_variant Exon 1 of 1
TRNS1unassigned_transcript_4800 c.-114G>T upstream_gene_variant
COX1unassigned_transcript_4799 c.*183C>A downstream_gene_variant
TRNDunassigned_transcript_4801 c.*43C>A downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt

Frequencies

GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
0.0
AC:
2
Gnomad homoplasmic
AF:
0.000053
AC:
3
AN:
56433
Gnomad heteroplasmic
AF:
0.0
AC:
0
AN:
56433

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leigh syndrome Uncertain:1
Oct 17, 2019
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The NC_012920.1:m.7628C>A (YP_003024029.1:p.Pro15Thr) variant in MTCO2 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: no criteria -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Pathogenic
0.56
Hmtvar
Pathogenic
0.83
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Benign
-0.15
T
DEOGEN2
Benign
0.13
T
LIST_S2
Benign
0.71
T
MutationAssessor
Pathogenic
4.2
H
PROVEAN
Pathogenic
-7.8
D
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
GERP RS
5.2
Varity_R
0.42

Splicing

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: rs1603221045; hg19: chrM-7629; API