M-4315-A-G

Variant names:

• chrM-4315-A-G
• rs876661359
• unassigned_transcript_4790:c.53A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 9)
• Consequence: TRNI stop_retained
• Scores: Mitotip Benign 2.8
• Clinical Significance: Uncertain significance no assertion criteria provided U:1 O:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.570

Genes affected

TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

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]

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNI	unassigned_transcript_4790	c.53A>G	p.Ter18Ter	stop_retained_variant	Exon 1 of 1
ND2	unassigned_transcript_4793	c.-155A>G		upstream_gene_variant
TRNM	unassigned_transcript_4792	c.-87A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.00010 AC: 9

Gnomad homoplasmic AF: 0.00012 AC: 7 AN: 56423

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56423

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2014

Stanford Center for Inherited Cardiovascular Disease, Stanford University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. MTTI m.4315A>G Based on the data reviewed below we consider this a variant of uncertain significance. G This variant is novel; it has not been previously reported in peer reviewed literature. However several variants in this gene (m4298G>A, m.4300A>G, m.4317A>G, m.4317delA) have been reported in association with chronic progressive external ophthalmoplegia (CPEO) and/or HCM. The residue in the MT-TI gene is not conserved across mammalian species. The nucleic acid change is predicted to have no affect on the secondary structure of the t RNA-Ile. This variant was not reported in 2704 individuals in mtDB (www.genpath.uu.se/mtDB), 3735 individuals in MitoWheel (http://mitowheel.org/mitowheel.html). -

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpretted as Uncertain significance and reported on 06-11-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.8
Hmtvar	Benign	0.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs876661359; hg19: chrM-4316;