M-10197-GCC-ACT

Variant names:

• chrM-10197-GCC-ACT
• ENST00000361227.2:c.139_141delGCCinsACT
• MT-ND3 p.Ala47Thr

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PS1_Very_Strong PM2

The ENST00000361227.2(MT-ND3):​c.139_141delGCCinsACT​(p.Ala47Thr) variant causes a missense change. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-ND3 ENST00000361227.2 missense
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: 4.76
• Publications: 0 publications found

Genes affected

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]

TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)

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: Pathogenic. The variant received 10 ACMG points.

• PS1: Transcript ENST00000361227.2 (MT-ND3) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: No frequency data in Mitomap. Probably very rare.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361227.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND3	ENST00000361227.2	TSL:6	c.139_141delGCCinsACT	p.Ala47Thr	missense	N/A	ENSP00000355206.2	P03897
	MT-CO3	ENST00000362079.2	TSL:6	c.*207_*209delGCCinsACT		downstream_gene	N/A	ENSP00000354982.2	P00414
	MT-TR	ENST00000387439.1	TSL:6	n.-208_-206delGCCinsACT		upstream_gene	N/A

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrM-10198;