M-1644-G-T

Variant names:

• chrM-1644-G-T
• rs587776441
• unassigned_transcript_4786:c.43G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000000000(TRNV):​c.43G>T​(p.Asp15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNV ENST00000000000 missense
• Scores: Mitotip Uncertain 13
• Clinical Significance: not provided no classification provided O:1 Leigh-Syndrome-/-HCM-/-MELAS,Adult-Leigh-Syndrome
• Conservation: PhyloP100: 0.980
• Publications: 0 publications found

Genes affected

TRNV (HGNC:7500): (mitochondrially encoded tRNA valine)

MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR1 (HGNC:7470): (mitochondrially encoded 12S RNA) Enables DNA binding activity and DNA-binding transcription factor binding activity. Involved in several processes, including osteoblast proliferation; regulation of carbohydrate utilization; and regulation of phosphate metabolic process. Located in extracellular space; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNV	unassigned_transcript_4786	c.43G>T	p.Asp15Tyr	missense_variant	Exon 1 of 1
RNR2	unassigned_transcript_4787	n.-27G>T		upstream_gene_variant
RNR1	unassigned_transcript_4785	n.*43G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TV	ENST00000387342.1	n.43G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-RNR2	ENST00000387347.2	n.-27G>T		upstream_gene_variant		6
MT-RNR1	ENST00000389680.2	n.*43G>T		downstream_gene_variant		6

Frequencies

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

Mitomap

Disease(s): Leigh-Syndrome-/-HCM-/-MELAS,Adult-Leigh-Syndrome

Status: Cfrm-[LP],Reported

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Leigh syndrome Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Benign	0.35
PhyloP100		0.98

Other links and lift over

dbSNP: rs587776441; hg19: chrM-1646;