rs199474828

chrM-8041-AAT-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The ENST00000361739.1(MT-CO2):c.458_459del(p.Met153AsnfsTer?) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO2 ENST00000361739.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1 Lactic-Acidosis
• Conservation: PhyloP100: 7.66

Genes affected

COX2 (HGNC:):

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.332 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-8041-AAT-A is Pathogenic according to our data. Variant chrM-8041-AAT-A is described in ClinVar as [Pathogenic]. Clinvar id is 9661.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX2	COX2.1	c.458_459del	p.Met153AsnfsTer?	frameshift_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO2	ENST00000361739.1	c.458_459del	p.Met153AsnfsTer?	frameshift_variant	1/1			P1

Frequencies

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap

Lactic-Acidosis

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial complex IV deficiency, nuclear type 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 22, 2001

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199474828; hg19: chrM-8042;