ENST00000361624.2:c.586C>G

Variant names:

• chrM-6489-C-G
• rs28461189
• ENST00000361624.2:c.586C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361624.2(MT-CO1):​c.586C>G​(p.Leu196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L196I) has been classified as Likely benign.

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Benign 0.20
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: 0.0840
• Publications: 16 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• BP4: Apogee2 supports a benign effect, 0.20073535 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.586C>G	p.Leu196Val	missense_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO1	ENST00000361624.2	c.586C>G	p.Leu196Val	missense_variant	Exon 1 of 1	6		ENSP00000354499.2

Frequencies

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

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.20
Hmtvar	Pathogenic	0.71
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.053	T
DEOGEN2	Benign	0.13	T
LIST_S2	Uncertain	0.86	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.084
PROVEAN	Benign	-2.3	N
Sift4G	Uncertain	0.018	D
GERP RS		1.1
Varity_R		0.60
Mutation Taster		=55/45	polymorphism

Other links and lift over

dbSNP: rs28461189; hg19: chrM-6490;