M-4688-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The ENST00000361453.3(MT-ND2):​c.219T>C​(p.Ala73Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0067 (AC: 410)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 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: Benign. The variant received -11 ACMG points.

• BP6: Variant M-4688-T-C is Benign according to our data. Variant chrM-4688-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 235516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-20 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0067000003
• BS2: High AC in GnomadMitoHomoplasmic at 325

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.219T>C	p.Ala73Ala	synonymous	Exon 1 of 1	ENSP00000355046.4	P03891
	MT-TM	ENST00000387377.1	TSL:6	n.*219T>C		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0067 AC: 410

Gnomad homoplasmic AF: 0.0058 AC: 325 AN: 56412

Gnomad heteroplasmic AF: 0.00016 AC: 9 AN: 56412

Alfa AF: 0.00671 Hom.: 30

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-20
Mutation Taster		=96/4	polymorphism

Other links and lift over

dbSNP: rs878853056; hg19: chrM-4689;