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 reviewed by expert panel B:4 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 reviewed_by_expert_panel, 3 stars.
• BP7: Synonymous conserved (PhyloP=-5.07 with no splicing effect.
• BA1: High frequency in mitomap database: 0.13859999

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361567.2. 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-ND5	ENST00000361567.2	TSL:6	c.36G>A	p.Leu12Leu	synonymous	Exon 1 of 1	ENSP00000354813.2	P03915
	MT-ND4	ENST00000361381.2	TSL:6	c.*235G>A		downstream_gene	N/A	ENSP00000354961.2	P03905
	MT-TH	ENST00000387441.1	TSL:6	n.*166G>A		downstream_gene	N/A

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

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	Mitochondrial disease (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

dbSNP: rs2853499; hg19: chrM-12373;