M-4373-T-C

Position:

• chrM-4373-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 11)
• Consequence: TRNQ missense
• Scores: Mitotip Uncertain 9.4
• Clinical Significance: Benign criteria provided, single submitter B:1 Tic-disorder-/-possibly-LVNC-associated
• Conservation: PhyloP100: 2.07

Genes affected

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

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

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

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-4373-T-C is Benign according to our data. Variant chrM-4373-T-C is described in ClinVar as [Benign]. Clinvar id is 689896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 12

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNQ	unassigned_transcript_4791	c.28A>G	p.Arg10Gly	missense_variant	1/1
TRNM	unassigned_transcript_4792	c.-29T>C		upstream_gene_variant
TRNI	unassigned_transcript_4790	c.*42T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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: 0.00020 AC: 11

Gnomad homoplasmic AF: 0.00021 AC: 12 AN: 56434

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56434

Mitomap

Tic-disorder-/-possibly-LVNC-associated

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome 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.4373T>C variant in MT-TQ gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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	Uncertain	9.4
Hmtvar	Benign	0.050

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603219432; hg19: chrM-4374;