rs2853499

Variant names:

• chrM-12372-G-A
• rs2853499
• ENST00000361567.2:c.36G>A

Your query was ambiguous. Multiple possible variants found:

• chrM-12372-G-A
• chrM-12372-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The ENST00000361567.2(MT-ND5):​c.36G>A​(p.Leu12Leu) 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 0.14 (AC: 8474)
• Consequence: MT-ND5 ENST00000361567.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 Altered-brain-pH-/-sCJD-patients
• Conservation: PhyloP100: -5.07
• Publications: 31 publications found

Genes affected

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) 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; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant M-12372-G-A is Benign according to our data. Variant chrM-12372-G-A is described in ClinVar as Benign. ClinVar VariationId is 522717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.07 with no splicing effect.
• BA1: High frequency in mitomap database: 0.13859999

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 1
ND4	unassigned_transcript_4811	c.*235G>A		downstream_gene_variant
TRNL2	unassigned_transcript_4814	c.*36G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND5	ENST00000361567.2	c.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354813.2
MT-ND4	ENST00000361381.2	c.*235G>A		downstream_gene_variant		6		ENSP00000354961.2

Frequencies

Mitomap GenBank AF: 0.14 AC: 8474

Gnomad homoplasmic AF: 0.16 AC: 8901 AN: 56353

Gnomad heteroplasmic AF: 0.00014 AC: 8 AN: 56353

Alfa AF: 0.117 Hom.: 1300

Mitomap

Disease(s): Altered-brain-pH-/-sCJD-patients

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial disease Benign:1

Jul 20, 2024

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.1
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs2853499; hg19: chrM-12373;