rs1569484165

Variant names:

• chrM-7661-C-CCCA
• rs1569484165
• ENST00000361739.1:c.76_77insCCA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The ENST00000361739.1(MT-CO2):​c.76_77insCCA​(p.His26delinsProAsn) variant causes a disruptive inframe insertion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO2 ENST00000361739.1 disruptive_inframe_insertion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 8.98
• Publications: 0 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-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]

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

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

TRND Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• PM2: No frequency data in Mitomap. Probably very rare.
• PM4: Nonframeshift variant in NON repetitive region in ENST00000361739.1. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant M-7661-C-CCCA is Pathogenic according to our data. Variant chrM-7661-C-CCCA is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 590892.Status of the report is no_assertion_criteria_provided, 0 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

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-CO2	ENST00000361739.1	TSL:6	c.76_77insCCA	p.His26delinsProAsn	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000354876.1	P00403
	MT-CO1	ENST00000361624.2	TSL:6	c.*216_*217insCCA		downstream_gene	N/A	ENSP00000354499.2	P00395
	MT-TS1	ENST00000387416.2	TSL:6	n.-148_-147insTGG		upstream_gene	N/A

Frequencies

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

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Abnormal aortic valve physiology (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Other links and lift over

dbSNP: rs1569484165; hg19: chrM-7662;