M-4640-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The ENST00000361453.3(MT-ND2):​c.171C>T​(p.Ile57Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I57I) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 11)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -9.19
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=-9.19 with no splicing effect.

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>T	p.Ile57Ile	synonymous	Exon 1 of 1	ENSP00000355046.4	P03891
	MT-TQ	ENST00000387372.1	TSL:6	n.-240G>A		upstream_gene	N/A
	MT-TM	ENST00000387377.1	TSL:6	n.*171C>T		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00020 AC: 11

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-9.2
Mutation Taster		=87/113	disease causing

Other links and lift over

dbSNP: rs387906426; hg19: chrM-4641;