ENST00000361453.3:c.219T>A

Variant names:

• chrM-4688-T-A
• rs878853056
• ENST00000361453.3:c.219T>A

Variant summary

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

The ENST00000361453.3(MT-ND2):​c.219T>A​(p.Ala73Ala) 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. A73A) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 5)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -20.0
• Publications: 5 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]

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=-20 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND2	unassigned_transcript_4793	c.219T>A	p.Ala73Ala	synonymous_variant	Exon 1 of 1
TRNM	unassigned_transcript_4792	c.*219T>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.219T>A	p.Ala73Ala	synonymous_variant	Exon 1 of 1	6		ENSP00000355046.4
MT-TM	ENST00000387377.1	n.*219T>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00010 AC: 5

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-20

Other links and lift over

dbSNP: rs878853056; hg19: chrM-4689;