chrM-10044-A-G

Variant names:

• chrM-10044-A-G
• rs41362547
• unassigned_transcript_4807:c.54A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000000000(TRNG):​c.54A>G​(p.Thr18Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0030 (AC: 185)
• Consequence: TRNG ENST00000000000 synonymous
• Scores: Mitotip Uncertain 11
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 SIDS
• Conservation: PhyloP100: -0.125
• Publications: 3 publications found

Genes affected

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

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]

MT-CO3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 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 VariationId is 9613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.125 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 397

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNG	unassigned_transcript_4807	c.54A>G	p.Thr18Thr	synonymous_variant	Exon 1 of 1
ND3	unassigned_transcript_4808	c.-15A>G		upstream_gene_variant
COX3	unassigned_transcript_4806	c.*54A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TG	ENST00000387429.1	n.54A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-ND3	ENST00000361227.2	c.-15A>G		upstream_gene_variant		6		ENSP00000355206.2
MT-CO3	ENST00000362079.2	c.*54A>G		downstream_gene_variant		6		ENSP00000354982.2

Frequencies

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

Disease(s): SIDS

Status: Unclear

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sudden death Pathogenic:1

May 09, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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.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
PhyloP100		-0.13

Other links and lift over

dbSNP: rs41362547; hg19: chrM-10045;