chrM-10040-C-T

Position:

• chrM-10040-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000387429.1(MT-TG):​n.50C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 6)
• Consequence: MT-TG ENST00000387429.1 non_coding_transcript_exon
• Scores: Mitotip Benign 7.4
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.619

Genes affected

MT-TG (HGNC:7486): (mitochondrially encoded tRNA glycine)

TRNG (HGNC:):

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-10040-C-T is Benign according to our data. Variant chrM-10040-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 690105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNG	TRNG.1	n.50C>T		non_coding_transcript_exon_variant	1/1
COX3	COX3.1			downstream_gene_variant			YP_003024032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TG	ENST00000387429.1	n.50C>T		non_coding_transcript_exon_variant	1/1
MT-ND3	ENST00000361227.2			upstream_gene_variant				ENSP00000355206	P1
MT-CO3	ENST00000362079.2			downstream_gene_variant				ENSP00000354982	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: 0.00010 AC: 6

Gnomad homoplasmic AF: 0.00016 AC: 9 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Alfa AF: 0.000446 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely 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.10040C>T variant in MT-TG gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BP4, BP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	7.4
Hmtvar	Benign	0.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603222642; hg19: chrM-10041;