chrM-9947-G-A

Variant names:

• chrM-9947-G-A
• rs370688668
• ENST00000362079.2:c.741G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The ENST00000362079.2(MT-CO3):​c.741G>A​(p.Val247Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0087 (AC: 532)
• Consequence: MT-CO3 ENST00000362079.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -9.24
• Publications: 2 publications found

Genes affected

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-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]

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

TRNG Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant M-9947-G-A is Benign according to our data. Variant chrM-9947-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.24 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0087
• BS2: High AC in GnomadMitoHomoplasmic at 482

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.741G>A	p.Val247Val	synonymous_variant	Exon 1 of 1
ND3	unassigned_transcript_4808	c.-112G>A		upstream_gene_variant
TRNG	unassigned_transcript_4807	c.-44G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.741G>A	p.Val247Val	synonymous_variant	Exon 1 of 1	6		ENSP00000354982.2
MT-ND3	ENST00000361227.2	c.-112G>A		upstream_gene_variant		6		ENSP00000355206.2
MT-TG	ENST00000387429.1	n.-44G>A		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0087 AC: 532

Gnomad homoplasmic AF: 0.0085 AC: 482 AN: 56411

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56411

Alfa AF: 0.00603 Hom.: 136

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 13, 2014

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-9.2
Mutation Taster		=90/10	polymorphism

Other links and lift over

dbSNP: rs370688668; hg19: chrM-9948;