rs199474826

Variant names:

• chrM-8009-G-A
• rs199474826
• ENST00000361739.1:c.424G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The ENST00000361739.1(MT-CO2):​c.424G>A​(p.Val142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict 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. V142A) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: MT-CO2 ENST00000361739.1 missense
• Scores: Apogee2 Benign 0.035
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.257
• Publications: 7 publications found

Genes affected

MT-CO2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• cytochrome-c oxidase deficiency disease

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

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

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.034805417 < 0.5 .
• BP6: Variant M-8009-G-A is Benign according to our data. Variant chrM-8009-G-A is described in ClinVar as Benign. ClinVar VariationId is 9659.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361739.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO2	ENST00000361739.1	TSL:6	c.424G>A	p.Val142Met	missense	Exon 1 of 1	ENSP00000354876.1

Frequencies

Mitomap GenBank AF: 0.0 AC: 1

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56425

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56425

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Familial colorectal cancer (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.035
Hmtvar	Pathogenic	0.69
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.35	T
DEOGEN2	Benign	0.0025	T
LIST_S2	Uncertain	0.94	D
MutationAssessor	Benign	0.64	N
PhyloP100		0.26
PROVEAN	Benign	-0.17	N
Sift	Uncertain	0.0020	D
GERP RS		0.39
Varity_R		0.26
Mutation Taster		=79/21	polymorphism

Other links and lift over

dbSNP: rs199474826; hg19: chrM-8010;