rs387906426

Variant names:

• chrM-4640-C-A
• rs387906426
• ENST00000361453.3:c.171C>A

Your query was ambiguous. Multiple possible variants found:

• chrM-4640-C-A
• chrM-4640-C-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361453.3(MT-ND2):​c.171C>A​(p.Ile57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I57T) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.0039 (AC: 240)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.083
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 O:1 LHON-/-Epilepsy
• Conservation: PhyloP100: -9.19
• Publications: 20 publications found

Genes affected

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

TRNM Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.08323591 < 0.5 .
• BP6: Variant M-4640-C-A is Benign according to our data. Variant chrM-4640-C-A is described in ClinVar as Benign. ClinVar VariationId is 9718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 66

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361453.3. 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-ND2	ENST00000361453.3	TSL:6	c.171C>A	p.Ile57Met	missense	Exon 1 of 1	ENSP00000355046.4	P03891
	MT-TQ	ENST00000387372.1	TSL:6	n.-240G>T		upstream_gene	N/A
	MT-TM	ENST00000387377.1	TSL:6	n.*171C>A		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0039 AC: 240

Gnomad homoplasmic AF: 0.0012 AC: 66 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.00506 Hom.: 22

Mitomap

Disease(s): LHON-/-Epilepsy

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Leber optic atrophy (2)
-	-	1	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.083
Hmtvar	Pathogenic	0.70
AlphaMissense	Benign	0.16
PhyloP100		-9.2

Other links and lift over

dbSNP: rs387906426; hg19: chrM-4641;