M-4363-T-C

Position:

• chrM-4363-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000387372.1(MT-TQ):​n.38A>G 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 0.00090 (AC: 55)
• Consequence: MT-TQ ENST00000387372.1 non_coding_transcript_exon
• Scores: Mitotip Benign 3.9
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:2 Metabolic-syndrome-and-polycystic-ovary-syndrome-/-possibly-associated-w-DEAF-+-RP-+-dev-delay-/-hypertension-/-LHON
• Conservation: PhyloP100: -0.938

Genes affected

MT-TQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

TRNQ (HGNC:):

MT-TM (HGNC:7492): (mitochondrially encoded tRNA methionine)

MT-TI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant M-4363-T-C is Benign according to our data. Variant chrM-4363-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 72

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNQ	TRNQ.1	n.38A>G		non_coding_transcript_exon_variant	1/1
TRNM	TRNM.1			upstream_gene_variant
TRNI	TRNI.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TQ	ENST00000387372.1	n.38A>G		non_coding_transcript_exon_variant	1/1
MT-TM	ENST00000387377.1			upstream_gene_variant
MT-TI	ENST00000387365.1			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: 0.00090 AC: 55

Gnomad homoplasmic AF: 0.0013 AC: 72 AN: 56424

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56424

Alfa AF: 0.00202 Hom.: 70

Mitomap

Metabolic-syndrome-and-polycystic-ovary-syndrome-/-possibly-associated-w-DEAF-+-RP-+-dev-delay-/-hypertension-/-LHON

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Stanford Center for Inherited Cardiovascular Disease, Stanford University

Dec 18, 2012

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. MT-TQ m.4363 T>C Given the data reviewed below, we classify this variant as a variant of uncertain significance. This variant has not been reported in association with cardiomyopathy. It has been reported in association with other mitochondrial phenotypes but it has also been seen in controls. Wong et al (2002) reported the variant as homoplasmic in a 7yo girl with retinitis pigmentosa, hearing loss, and failure to thrive. Zhu et al (2009) repoted a decrase in oxygen consumptionm rate in cell lines with this variant. Abu-Amero et al (2008) observed the variant in a patient with psudoexfoliation syndrome and considered the variant not pathobenic. The variant has been seen in a total of 8 out of 12,830 individuals studies. It was observed in 1 of 2704 individuals in mtDB, 2 of 3735 individuals in MitoWheel. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Skane University Hospital Lund

Jan 04, 2023

- -

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

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.4363T>C variant in MT-TQ gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	3.9
Hmtvar	Pathogenic	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200009705; hg19: chrM-4364;