chrM-3252-A-T

Variant names:

• chrM-3252-A-T
• rs199474661
• unassigned_transcript_4788:c.23A>T

Variant summary

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

The ENST00000000000(TRNL1):​c.23A>T​(p.Asn8Ile) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNL1 ENST00000000000 missense
• Scores: Mitotip Uncertain 11
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 MELAS,EXIT
• Conservation: PhyloP100: 6.99
• Publications: 2 publications found

Genes affected

TRNL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

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-RNR2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED 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
TRNL1	unassigned_transcript_4788	c.23A>T	p.Asn8Ile	missense_variant	Exon 1 of 1
ND1	unassigned_transcript_4789	c.-55A>T		upstream_gene_variant
RNR2	unassigned_transcript_4787	n.*23A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TL1	ENST00000386347.1	n.23A>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-ND1	ENST00000361390.2	c.-55A>T		upstream_gene_variant		6		ENSP00000354687.2
MT-RNR2	ENST00000387347.2	n.*23A>T		downstream_gene_variant		6

Frequencies

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

Mitomap

Disease(s): MELAS,EXIT

Status: Reported,Reported

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Uncertain:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.3252A>T variant in MT-TL1 gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM2, PM9, PP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Benign	0.15
PhyloP100		7.0

Other links and lift over

dbSNP: rs199474661; hg19: chrM-3253;