rs199474825

chrM-7587-T-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP3 PP5

The ENST00000361739.1(MT-CO2):c.2T>C(p.Met1?) variant causes a start lost 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-CO2 ENST00000361739.1 start_lost
• Scores: Apogee2 Pathogenic 0.88
• Clinical Significance: Pathogenic no assertion criteria provided P:1 Mitochondrial-Encephalomyopathy
• Conservation: PhyloP100: 7.73

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]

MT-TD (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Apogee2 supports a deletorius effect, 0.8750365 >= 0.5 .
• PP5: Variant M-7587-T-C is Pathogenic according to our data. Variant chrM-7587-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 9658.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.2T>C	p.Met1?	start_lost	1/1
TRND	TRND.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO2	ENST00000361739.1	c.2T>C	p.Met1?	start_lost	1/1			P1
MT-TD	ENST00000387419.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

Mitochondrial-Encephalomyopathy

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

May 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.88
Hmtvar	Pathogenic	0.79
BayesDel_addAF	Benign	-0.020	T
DEOGEN2	Benign	0.23	T
LIST_S2	Uncertain	0.90	D
MutationTaster	Benign	1.0	A
PROVEAN	Pathogenic	-5.7	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
GERP RS		4.3
Varity_R		0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199474825; hg19: chrM-7588;