chrM-6299-A-G

Variant names:

• chrM-6299-A-G
• rs1057520195
• ENST00000361624.2:c.396A>G
• MT-CO1 p.Leu132Leu

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361624.2(MT-CO1):​c.396A>G​(p.Leu132Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 8)
• Consequence: MT-CO1 ENST00000361624.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.513
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=0.513 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 9

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.396A>G	p.Leu132Leu	synonymous	Exon 1 of 1	ENSP00000354499.2	P00395

Frequencies

Mitomap GenBank AF: 0.00010 AC: 8

Gnomad homoplasmic AF: 0.00016 AC: 9 AN: 56428

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56428

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

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

Other links and lift over

dbSNP: rs1057520195;

hg19: chrM-6300;