rs1057516057

chrM-3275-C-AchrM-3275-C-GchrM-3275-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The ENST00000386347.1(MT-TL1):n.46C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: MT-TL1 ENST00000386347.1 non_coding_transcript_exon
• Scores: Mitotip Benign 2.0
• Clinical Significance: Likely benign criteria provided, single submitter B:1 LHON,Metabolic-syndrome-and-polycystic-ovary-syndrome-/-LHON
• Conservation: PhyloP100: -3.37

Genes affected

MT-TL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

TRNL1 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-3275-C-A is Benign according to our data. Variant chrM-3275-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 689867.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNL1	TRNL1.1	n.46C>A		non_coding_transcript_exon_variant	1/1
RNR2	RNR2.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TL1	ENST00000386347.1	n.46C>A		non_coding_transcript_exon_variant	1/1
MT-ND1	ENST00000361390.2			upstream_gene_variant				P1
MT-RNR2	ENST00000387347.2			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 GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

LHON,Metabolic-syndrome-and-polycystic-ovary-syndrome-/-LHON

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Jul 12, 2019

The NC_012920.1:m.3275C>A variant in MT-TL1 gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.0
Hmtvar	Benign	0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057516057; hg19: chrM-3276;