chrM-5465-T-C

Variant names:

• chrM-5465-T-C
• rs3902405
• ENST00000361453.3:c.996T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The ENST00000361453.3(MT-ND2):​c.996T>C​(p.Leu332Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.038 (AC: 2310)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -7.03
• Publications: 7 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]

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNA 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-5465-T-C is Benign according to our data. Variant chrM-5465-T-C is described in ClinVar as [Benign]. Clinvar id is 235745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-7.03 with no splicing effect.
• BA1: High frequency in mitomap database: 0.0378

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND2	unassigned_transcript_4793	c.996T>C	p.Leu332Leu	synonymous_variant	Exon 1 of 1
TRNW	unassigned_transcript_4794	c.-47T>C		upstream_gene_variant
TRNN	unassigned_transcript_4796	c.*192A>G		downstream_gene_variant
TRNA	unassigned_transcript_4795	c.*122A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.996T>C	p.Leu332Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000355046.4
MT-TW	ENST00000387382.1	n.-47T>C		upstream_gene_variant		6
MT-TA	ENST00000387392.1	n.*122A>G		downstream_gene_variant		6
MT-TN	ENST00000387400.1	n.*192A>G		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.038 AC: 2310

Gnomad homoplasmic AF: 0.0032 AC: 178 AN: 56431

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56431

Alfa AF: 0.00273 Hom.: 72

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 02, 2015

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-7.0
Mutation Taster		=97/3	polymorphism

Other links and lift over

dbSNP: rs3902405; hg19: chrM-5466;