M-9301-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.95C>T​(p.Ala32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A32T) has been classified as Benign.

Frequency

Mitomap GenBank:
𝑓 0.00040 ( AC: 23 )

Consequence

MT-CO3
ENST00000362079.2 missense

Scores

Apogee2
Benign
0.074

Clinical Significance

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

Conservation

PhyloP100: -1.53
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Apogee2 supports a benign effect, 0.07441712 < 0.5 .
BP6
Variant M-9301-C-T is Benign according to our data. Variant chrM-9301-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 693142.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomadMitoHomoplasmic at 19

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COX3COX3.1 use as main transcriptc.95C>T p.Ala32Val missense_variant 1/1 YP_003024032.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-CO3ENST00000362079.2 linkuse as main transcriptc.95C>T p.Ala32Val missense_variant 1/1 ENSP00000354982 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:
23
Gnomad homoplasmic
AF:
0.00034
AC:
19
AN:
56433
Gnomad heteroplasmic
AF:
0.000035
AC:
2
AN:
56433

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.9301C>T (YP_003024032.1:p.Ala32Val) 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, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.074
Hmtvar
Benign
0.080
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.52
T
DEOGEN2
Benign
0.0039
T
LIST_S2
Benign
0.42
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
N
PROVEAN
Benign
0.50
N
Sift
Benign
0.41
T
Sift4G
Benign
0.73
T
GERP RS
-5.9
Varity_R
0.061

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: rs1603222227; hg19: chrM-9302; API