chrM-9234-A-G

Position:

Variant summary

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

The ENST00000362079.2(MT-CO3):ā€‹c.28A>Gā€‹(p.Met10Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Mitomap GenBank:
š‘“ 0.00010 ( AC: 5 )

Consequence

MT-CO3
ENST00000362079.2 missense

Scores

Apogee2
Benign
0.15

Clinical Significance

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

Conservation

PhyloP100: 7.16
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Apogee2 supports a benign effect, 0.14856704 < 0.5 .
BP6
Variant M-9234-A-G is Benign according to our data. Variant chrM-9234-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 693130.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 8

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COX3COX3.1 use as main transcriptc.28A>G p.Met10Val 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.28A>G p.Met10Val 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:
0.00010
AC:
5
Gnomad homoplasmic
AF:
0.00014
AC:
8
AN:
56432
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56432
Alfa
AF:
0.000223
Hom.:
1

Mitomap

No disease associated.

ClinVar

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

Submissions by phenotype

Leigh syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The NC_012920.1:m.9234A>G (YP_003024032.1:p.Met10Val) variant in MTCO3 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BP5 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.15
Hmtvar
Pathogenic
0.47
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.23
T
MutationTaster
Benign
1.0
N
GERP RS
5.0
Varity_R
0.39

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: rs1603222190; hg19: chrM-9235; API