rs41347846

Variant names:

• chrM-10034-T-C
• rs41347846
• unassigned_transcript_4807:c.44T>C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Mitomap GenBank: 𝑓 0.016 (AC: 991)
• Consequence: TRNG missense
• Scores: Mitotip Benign 3.0
• Clinical Significance: Benign reviewed by expert panel B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.35

Genes affected

TRNG (HGNC:7486): (mitochondrially encoded tRNA glycine)

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]

COX3 (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 -16 ACMG points.

• BP6: Variant M-10034-T-C is Benign according to our data. Variant chrM-10034-T-C is described in ClinVar as [Benign]. Clinvar id is 690104.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: High frequency in mitomap database: 0.0162

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNG	unassigned_transcript_4807	c.44T>C	p.Val15Ala	missense_variant	Exon 1 of 1
ND3	unassigned_transcript_4808	c.-25T>C		upstream_gene_variant
COX3	unassigned_transcript_4806	c.*44T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.016 AC: 991

Gnomad homoplasmic AF: 0.018 AC: 1008 AN: 56428

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56428

Alfa AF: 0.0259 Hom.: 1106

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

Submissions by phenotype

Mitochondrial disease Benign:1

Mar 24, 2022

ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The m.10034T>C variant in MT-TG was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is associated with haplogroup I (almost 100% of individuals in this haplogroup have this variant) and the overall allele frequency in the GenBank database is 1.553% (BA1). Additionally, the computational predictor MitoTIP suggests this variant is benign (6.7th percentile) and HmtVAR predicts it to be polymorphic (BP4). In summary, this variant meets criteria to be classified as benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4. -

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.10034T>C variant in MT-TG 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: BA1, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	3.0
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: rs41347846; hg19: chrM-10035;