rs41413745

Variant names:

• chrM-6734-G-A
• rs41413745
• ENST00000361624.2:c.831G>A
• MT-CO1 p.Met277Met

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The ENST00000361624.2(MT-CO1):​c.831G>A​(p.Met277Met) variant causes a synonymous 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 0.0070 (AC: 426)
• Consequence: MT-CO1 ENST00000361624.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.05
• Publications: 7 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: Benign. The variant received -17 ACMG points.

• BP6: Variant M-6734-G-A is Benign according to our data. Variant chrM-6734-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0069999998
• BS2: High AC in GnomadMitoHomoplasmic at 481

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.831G>A	p.Met277Met	synonymous	Exon 1 of 1	ENSP00000354499.2	P00395

Frequencies

Mitomap GenBank AF: 0.0070 AC: 426

Gnomad homoplasmic AF: 0.0085 AC: 481 AN: 56419

Gnomad heteroplasmic AF: 0.00011 AC: 6 AN: 56419

Alfa AF: 0.00895 Hom.: 394

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
DEOGEN2	Benign	0.11	T
LIST_S2	Pathogenic	0.98	D
MutationAssessor	Benign	1.9	L
PhyloP100		-1.1
PROVEAN	Uncertain	-2.8	D
Varity_R		0.66

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41413745;

hg19: chrM-6735;