rs41362547

Positions:

• chrM-10044-A-G

Variant summary

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

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

• Frequency: Mitomap GenBank: 𝑓 0.0030 (AC: 185)
• Consequence: TRNG synonymous
• Scores: Mitotip Uncertain 11
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 SIDS
• Conservation: PhyloP100: -0.125

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-10044-A-G is Benign according to our data. Variant chrM-10044-A-G is described in ClinVar as [Benign]. Clinvar id is 9613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 397

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNG	unassigned_transcript_4807	c.54A>G	p.Thr18Thr	synonymous_variant	1/1
ND3	unassigned_transcript_4808	c.-15A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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: 0.0030 AC: 185

Gnomad homoplasmic AF: 0.0070 AC: 397 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.00558 Hom.: 25

Mitomap

SIDS

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sudden death Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 09, 2003

- -

MELAS syndrome 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.10044A>G variant in MT-TG gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41362547; hg19: chrM-10045;