chrM-7275-T-C

Variant names:

• chrM-7275-T-C
• rs267606884
• ENST00000361624.2:c.1372T>C
• MT-CO1 p.Ser458Pro

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The ENST00000361624.2(MT-CO1):​c.1372T>C​(p.Ser458Pro) variant causes a missense 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 Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Pathogenic 0.68
• Clinical Significance: Pathogenic no assertion criteria provided P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.73
• Publications: 5 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]

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRNS1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Apogee2 supports a deletorius effect, 0.6811576 >= 0.5 .
• PP5: Variant M-7275-T-C is Pathogenic according to our data. Variant chrM-7275-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 9673.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1372T>C	p.Ser458Pro	missense	Exon 1 of 1	ENSP00000354499.2	P00395
	MT-TD	ENST00000387419.1	TSL:6	n.-243T>C		upstream_gene	N/A
	MT-TS1	ENST00000387416.2	TSL:6	n.*171A>G		downstream_gene	N/A

Frequencies

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

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.68
Hmtvar	Pathogenic	0.86
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.055	T
DEOGEN2	Benign	0.18	T
LIST_S2	Uncertain	0.95	D
MutationAssessor	Pathogenic	4.7	H
PhyloP100		7.7
PROVEAN	Benign	-1.7	N
Sift4G	Uncertain	0.0030	D
Varity_R		0.96

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

Other links and lift over

dbSNP: rs267606884;

hg19: chrM-7276;