M-9276-G-A

Position:

• chrM-9276-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000362079.2(MT-CO3):​c.70G>A​(p.Ala24Thr) 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 Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 10)
• Consequence: MT-CO3 ENST00000362079.2 missense
• Scores: Apogee2 Benign 0.12
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 3.35

Genes affected

COX3 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.12465833 < 0.5 .
• BP6: Variant M-9276-G-A is Benign according to our data. Variant chrM-9276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 693136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 15

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX3	COX3.1	c.70G>A	p.Ala24Thr	missense_variant	1/1		YP_003024032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.70G>A	p.Ala24Thr	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: 0.00020 AC: 10

Gnomad homoplasmic AF: 0.00027 AC: 15 AN: 56421

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56421

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Oct 17, 2019

The NC_012920.1:m.9276G>A (YP_003024032.1:p.Ala24Thr) 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: BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.12
Hmtvar	Benign	0.16
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.30	T
DEOGEN2	Benign	0.069	T
LIST_S2	Benign	0.70	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N
PROVEAN	Uncertain	-2.7	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.048	D
GERP RS		5.0
Varity_R		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1603222209; hg19: chrM-9277;