M-7443-A-C

Variant names:

• chrM-7443-A-C
• rs397507452
• ENST00000361624.2:c.1540A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000361624.2(MT-CO1):​c.1540A>C​(p.Ter514Argext*?) variant causes a stop lost, splice region change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position has been classified as Pathogenic.

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO1 ENST00000361624.2 stop_lost, splice_region
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -0.146
• Publications: 0 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]

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]

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.
• PM4: Stoplost variant in ENST00000361624.2 Downstream stopcodon found after 5 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.1540A>C	p.Ter514Argext*?	stop_lost, splice_region_variant	Exon 1 of 1
COX2	unassigned_transcript_4802	c.-143A>C		upstream_gene_variant
TRND	unassigned_transcript_4801	c.-75A>C		upstream_gene_variant
TRNS1	unassigned_transcript_4800	c.*3T>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO1	ENST00000361624.2	c.1540A>C	p.Ter514Argext*?	stop_lost, splice_region_variant	Exon 1 of 1	6		ENSP00000354499.2
MT-CO2	ENST00000361739.1	c.-143A>C		upstream_gene_variant		6		ENSP00000354876.1
MT-TD	ENST00000387419.1	n.-75A>C		upstream_gene_variant		6
MT-TS1	ENST00000387416.2	n.*3T>G		downstream_gene_variant		6

Frequencies

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

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15
Mutation Taster		=97/3	polymorphism

Other links and lift over

dbSNP: rs397507452; hg19: chrM-7444;