M-4372-C-T

Position:

• chrM-4372-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP5_Strong

The ENST00000387372.1(MT-TQ):​n.29G>A variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TQ ENST00000387372.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 16
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 Suspected-mito-disease
• Conservation: PhyloP100: 3.75

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-4372-C-T is Pathogenic according to our data. Variant chrM-4372-C-T is described in ClinVar as [Uncertain_significance]. Clinvar id is 689895.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNQ	TRNQ.1	n.29G>A		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.29G>A		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

Suspected-mito-disease

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely pathogenic, 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.4372C>T variant in MT-TQ gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM2 PM9, PP3, PP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	16
Hmtvar	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603219429; hg19: chrM-4373;