M-3242-G-A

Position:

• chrM-3242-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2 PP5_Very_Strong

The ENST00000386347.1(MT-TL1):​n.13G>A variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TL1 ENST00000386347.1 non_coding_transcript_exon
• Scores: Mitotip Benign 7.0
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:3 MM-/-HCM+renal-tubular-dysfunction
• Conservation: PhyloP100: 4.54

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-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 Pathogenic. Variant got 10 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-3242-G-A is Pathogenic according to our data. Variant chrM-3242-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNL1	TRNL1.1	n.13G>A		non_coding_transcript_exon_variant	1/1
RNR2	RNR2.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TL1	ENST00000386347.1	n.13G>A		non_coding_transcript_exon_variant	1/1
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: 0

Mitomap

MM-/-HCM+renal-tubular-dysfunction

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MELAS syndrome Pathogenic:2

Likely pathogenic, 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.3242G>A variant in MT-TL1 gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PS5, PM9, PM10 -
Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Myelodysplastic syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 11, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	7.0
Hmtvar	Pathogenic	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193303018; hg19: chrM-3243;