M-12396-T-C

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND5	ENST00000361567.2	TSL:6	c.60T>C	p.Leu20Leu	synonymous	Exon 1 of 1	ENSP00000354813.2
	MT-TH	ENST00000387441.1	TSL:6	n.*190T>C		downstream_gene	N/A
	MT-TS2	ENST00000387449.1	TSL:6	n.*131T>C		downstream_gene	N/A

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 v4.9

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

Other links and lift over

dbSNP: rs200890363; hg19: chrM-12397;