rs387906731

Variant names:

• chrM-10450-A-G
• rs387906731
• unassigned_transcript_4809:c.46A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000000000(TRNR):​c.46A>G​(p.Met16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: TRNR ENST00000000000 missense
• Scores: Mitotip Uncertain 15
• Clinical Significance: Uncertain significance reviewed by expert panel P:2 U:1 Combined-OXPHOS-defects-&-severe-multisystem-disorder
• Conservation: PhyloP100: 0.362
• Publications: 1 publications found

Genes affected

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

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [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]

MT-ND3 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber plus disease

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• maternally-inherited Leigh syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387439.1. 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-TR	ENST00000387439.1	TSL:6	n.46A>G		non_coding_transcript_exon	Exon 1 of 1
	MT-ND4L	ENST00000361335.1	TSL:6	c.-20A>G		upstream_gene	N/A	ENSP00000354728.1	P03901
	MT-ND3	ENST00000361227.2	TSL:6	c.*46A>G		downstream_gene	N/A	ENSP00000355206.2	P03897

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Alfa AF: 0.00 Hom.: 0

Mitomap

Disease(s): Combined-OXPHOS-defects-&-severe-multisystem-disorder

Status: Reported

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
1	1	-	Mitochondrial disease (2)
1	-	-	Mitochondrial encephalomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Pathogenic	0.65
PhyloP100		0.36

Other links and lift over

dbSNP: rs387906731; hg19: chrM-10451;