M-5953-CA-C

Variant summary

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

The ENST00000361624.2(MT-CO1):c.51del(p.Leu18TyrfsTer?) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO1 ENST00000361624.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -3.52

Genes affected

COX1 (HGNC:):

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]

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. There are 4 pathogenic variants in the truncated region.
• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-5953-CA-C is Pathogenic according to our data. Variant chrM-5953-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 590893.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX1	COX1.1	c.51del	p.Leu18TyrfsTer?	frameshift_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO1	ENST00000361624.2	c.51del	p.Leu18TyrfsTer?	frameshift_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

No disease associated.

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Tetralogy of Fallot Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Molecular Biology Laboratory, University of Basrah

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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: rs1569484042; hg19: chrM-5954;