M-7547-T-C

Position:

• chrM-7547-T-C

Variant summary

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

The ENST00000387419.1(MT-TD):​n.30T>C variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00090 (AC: 56)
• Consequence: MT-TD ENST00000387419.1 non_coding_transcript_exon
• Scores: Mitotip Benign 4.4
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 5.99

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]

MT-TS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-7547-T-C is Benign according to our data. Variant chrM-7547-T-C is described in ClinVar as [Benign]. Clinvar id is 690044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 45

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRND	TRND.1	n.30T>C		non_coding_transcript_exon_variant	1/1
COX2	COX2.1			upstream_gene_variant			YP_003024029.1
TRNS1	TRNS1.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TD	ENST00000387419.1	n.30T>C		non_coding_transcript_exon_variant	1/1
MT-CO2	ENST00000361739.1			upstream_gene_variant				ENSP00000354876	P1
MT-TS1	ENST00000387416.2			upstream_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: 56

Gnomad homoplasmic AF: 0.00080 AC: 45 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Alfa AF: 0.000672 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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.7547T>C variant in MT-TD 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, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	4.4
Hmtvar	Pathogenic	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879076142; hg19: chrM-7548;