chrM-6264-G-A

Variant names:

• chrM-6264-G-A
• rs267606882
• ENST00000361624.2:c.361G>A

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000361624.2(MT-CO1):​c.361G>A​(p.Gly121*) variant causes a stop gained change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO1 ENST00000361624.2 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.69
• Publications: 2 publications found

Genes affected

MT-CO1 (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]

MT-CO1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• MELAS syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial non-syndromic sensorineural hearing loss

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 25 pathogenic variants in the truncated region.
• PM2: No frequency data in Mitomap. Probably very rare.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361624.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO1	ENST00000361624.2	TSL:6	c.361G>A	p.Gly121*	stop_gained	Exon 1 of 1	ENSP00000354499.2	P00395

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Alfa AF: 0.00 Hom.: 0

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Familial colorectal cancer (1)
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.42	D
DEOGEN2	Benign	0.22	T
LIST_S2	Pathogenic	0.99	D
MutationAssessor	Pathogenic	5.1	H
PhyloP100		7.7
PROVEAN	Pathogenic	-6.6	D
GERP RS		5.3
Varity_R		0.82
Mutation Taster		=12/88	disease causing

Other links and lift over

dbSNP: rs267606882; hg19: chrM-6265;