chrM-9211-C-T

Position:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The ENST00000362079.2(MT-CO3):​c.5C>T​(p.Thr2Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2A) has been classified as Benign.

Frequency

Mitomap GenBank:
𝑓 0.00040 ( AC: 26 )

Consequence

MT-CO3
ENST00000362079.2 missense

Scores

Apogee2
Benign
0.10

Clinical Significance

Benign criteria provided, single submitter B:1
No linked disesase in Mitomap

Conservation

PhyloP100: 3.20
Variant links:
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]
MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Apogee2 supports a benign effect, 0.10082931 < 0.5 .
BP6
Variant M-9211-C-T is Benign according to our data. Variant chrM-9211-C-T is described in ClinVar as [Benign]. Clinvar id is 693126.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 18

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COX3COX3.1 use as main transcriptc.5C>T p.Thr2Ile missense_variant 1/1 YP_003024032.1
ATP6ATP6.1 use as main transcript downstream_gene_variant YP_003024031.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-CO3ENST00000362079.2 linkuse as main transcriptc.5C>T p.Thr2Ile missense_variant 1/1 ENSP00000354982 P1
MT-ATP6ENST00000361899.2 linkuse as main transcript downstream_gene_variant ENSP00000354632 P1

Frequencies

GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
0.00040
AC:
26
Gnomad homoplasmic
AF:
0.00032
AC:
18
AN:
56431
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56431

Mitomap

No disease associated.

ClinVar

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

Submissions by phenotype

Leigh syndrome Benign:1
Benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The NC_012920.1:m.9211C>T (YP_003024032.1:p.Thr2Ile) variant in MTCO3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.10
Hmtvar
Benign
0.060
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Benign
-0.36
T
DEOGEN2
Benign
0.069
T
LIST_S2
Pathogenic
0.99
D
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
N
PROVEAN
Uncertain
-2.5
N
Sift
Uncertain
0.022
D
Sift4G
Pathogenic
0.0010
D
GERP RS
4.0
Varity_R
0.17

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: rs1603222177; hg19: chrM-9212; API