M-7650-C-T

Variant summary

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

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

Frequency

Mitomap GenBank:
𝑓 0.0 ( AC: 3 )

Consequence

COX2
missense

Scores

Apogee2
Benign
0.035

Clinical Significance

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

Conservation

PhyloP100: 2.39
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.65C>T p.Thr22Ile missense_variant Exon 1 of 1
TRNS1unassigned_transcript_4800 c.-136G>A upstream_gene_variant
COX1unassigned_transcript_4799 c.*205C>T downstream_gene_variant
TRNDunassigned_transcript_4801 c.*65C>T 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:
3
Gnomad homoplasmic
AF:
0.000053
AC:
3
AN:
56432
Gnomad heteroplasmic
AF:
0.0
AC:
0
AN:
56432
Alfa
AF:
0.000223
Hom.:
1

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.7650C>T (YP_003024029.1:p.Thr22Ile) 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: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.035
Hmtvar
Benign
0.17
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.38
T
DEOGEN2
Benign
0.022
T
LIST_S2
Benign
0.023
T
MutationAssessor
Benign
-0.55
N
PROVEAN
Benign
-0.95
N
Sift
Benign
0.17
T
Sift4G
Uncertain
0.016
D
GERP RS
-0.78
Varity_R
0.080

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: rs1603221063; hg19: chrM-7651; API