M-7566-G-A

Position:

• chrM-7566-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2 PP5_Very_Strong

The ENST00000387419.1(MT-TD):​n.49G>A variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TD ENST00000387419.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2 Unspecified-patient-from-clinical-lab
• Conservation: PhyloP100: 4.00

Genes affected

MT-TD (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

TRND (HGNC:):

MT-CO2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-7566-G-A is Pathogenic according to our data. Variant chrM-7566-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 690050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRND	TRND.1	n.49G>A		non_coding_transcript_exon_variant	1/1
COX2	COX2.1			upstream_gene_variant			YP_003024029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TD	ENST00000387419.1	n.49G>A		non_coding_transcript_exon_variant	1/1
MT-CO2	ENST00000361739.1			upstream_gene_variant				ENSP00000354876	P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56431

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56431

Mitomap

Unspecified-patient-from-clinical-lab

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

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.7566G>A variant in MT-TD 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	15
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: rs1603221016; hg19: chrM-7567;