M-9952-G-T

Variant names:

• chrM-9952-G-T
• rs267606613
• ENST00000362079.2:c.746G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000362079.2(MT-CO3):​c.746G>T​(p.Trp249Leu) variant causes a missense change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position has been classified as Likely pathogenic.

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO3 ENST00000362079.2 missense
• Scores: Apogee2 Uncertain 0.45
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: 7.73
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• BP4: Apogee2 supports a benign effect, 0.45119107 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.746G>T	p.Trp249Leu	missense_variant	Exon 1 of 1
ND3	unassigned_transcript_4808	c.-107G>T		upstream_gene_variant
TRNG	unassigned_transcript_4807	c.-39G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.746G>T	p.Trp249Leu	missense_variant	Exon 1 of 1	6		ENSP00000354982.2
MT-ND3	ENST00000361227.2	c.-107G>T		upstream_gene_variant		6		ENSP00000355206.2
MT-TG	ENST00000387429.1	n.-39G>T		upstream_gene_variant		6

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Uncertain	0.45
Hmtvar	Pathogenic	0.78
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.16	D
PhyloP100		7.7
GERP RS		5.1
Mutation Taster		=12/88	disease causing

Other links and lift over

dbSNP: rs267606613; hg19: chrM-9953;