M-4370-T-C

Position:

• chrM-4370-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000387372.1(MT-TQ):​n.31A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0023 (AC: 138)
• Consequence: MT-TQ ENST00000387372.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 9.5
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.547

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 -13 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-4370-T-C is Benign according to our data. Variant chrM-4370-T-C is described in ClinVar as [Benign]. Clinvar id is 689893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNQ	TRNQ.1	n.31A>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.31A>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: 0.0023 AC: 138

Gnomad homoplasmic AF: 0.013 AC: 748 AN: 56430

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56430

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 19, 2018

- -

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.4370T>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	9.5
Hmtvar	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603219427; hg19: chrM-4371;