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

Transcripts

RefSeq

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

Ensembl

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

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 12, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs878853056; hg19: chrM-4689;