rs2853487

Variant names:

• chrM-10589-G-A
• rs2853487
• ENST00000361335.1:c.120G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The ENST00000361335.1(MT-ND4L):​c.120G>A​(p.Leu40Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.032 (AC: 1938)
• Consequence: MT-ND4L ENST00000361335.1 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -3.89
• Publications: 12 publications found

Genes affected

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [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]

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-3.89 with no splicing effect.
• BA1: High frequency in mitomap database: 0.0317

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4L	unassigned_transcript_4810	c.120G>A	p.Leu40Leu	synonymous_variant	Exon 1 of 1
ND4	unassigned_transcript_4811	c.-171G>A		upstream_gene_variant
ND3	unassigned_transcript_4808	c.*185G>A		downstream_gene_variant
TRNR	unassigned_transcript_4809	c.*120G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND4L	ENST00000361335.1	c.120G>A	p.Leu40Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354728.1
MT-ND4	ENST00000361381.2	c.-171G>A		upstream_gene_variant		6		ENSP00000354961.2
MT-ND3	ENST00000361227.2	c.*185G>A		downstream_gene_variant		6		ENSP00000355206.2
MT-TR	ENST00000387439.1	n.*120G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.032 AC: 1938

Gnomad homoplasmic AF: 0.018 AC: 1039 AN: 56423

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56423

Alfa AF: 0.0181 Hom.: 796

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.9
Mutation Taster		=93/7	polymorphism

Other links and lift over

dbSNP: rs2853487; hg19: chrM-10590;