rs386829154

Variant names:

• chrM-12396-T-C
• rs200890363
• ENST00000361567.2:c.60T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361567.2(MT-ND5):​c.60T>C​(p.Leu20Leu) 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 0.00060 (AC: 35)
• Consequence: MT-ND5 ENST00000361567.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -20.0
• Publications: 6 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]

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: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=-20 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 13

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.60T>C	p.Leu20Leu	synonymous_variant	Exon 1 of 1
TRNL2	unassigned_transcript_4814	c.*60T>C		downstream_gene_variant
TRNH	unassigned_transcript_4812	c.*190T>C		downstream_gene_variant
TRNS2	unassigned_transcript_4813	c.*131T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND5	ENST00000361567.2	c.60T>C	p.Leu20Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354813.2
MT-TH	ENST00000387441.1	n.*190T>C		downstream_gene_variant		6
MT-TS2	ENST00000387449.1	n.*131T>C		downstream_gene_variant		6
MT-TL2	ENST00000387456.1	n.*60T>C		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00060 AC: 35

Gnomad homoplasmic AF: 0.00023 AC: 13 AN: 56429

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56429

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-20
Mutation Taster		=94/6	polymorphism

Other links and lift over

dbSNP: rs200890363; hg19: chrM-12397;