M-4375-C-T

Variant names:

• chrM-4375-C-T
• rs1603219433
• unassigned_transcript_4791:c.26G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 9)
• Consequence: TRNQ missense
• Scores: Mitotip Benign 6.4
• Clinical Significance: Likely benign criteria provided, single submitter B:1 Matrilineal-hypertension-risk-factor
• Conservation: PhyloP100: -0.254

Genes affected

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

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]

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant M-4375-C-T is Benign according to our data. Variant chrM-4375-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 689897.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNQ	unassigned_transcript_4791	c.26G>A	p.Arg9Gln	missense_variant	Exon 1 of 1
ND2	unassigned_transcript_4793	c.-95C>T		upstream_gene_variant
TRNM	unassigned_transcript_4792	c.-27C>T		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: 0.000035 AC: 2 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

Matrilineal-hypertension-risk-factor

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Benign:1

Jul 12, 2019

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.4375C>T variant in MT-TQ 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: BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	6.4
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: rs1603219433; hg19: chrM-4376;