chrM-12246-C-A

Variant names:

• chrM-12246-C-A
• rs28508189
• unassigned_transcript_4813:c.40C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000000000(TRNS2):​c.40C>A​(p.Leu14Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 4)
• Consequence: TRNS2 ENST00000000000 missense
• Scores: Mitotip Benign 2.4
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 CIPO
• Conservation: PhyloP100: -4.64
• Publications: 0 publications found

Genes affected

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

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)

TRNH Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387449.1. 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-TS2	ENST00000387449.1	TSL:6	n.40C>A		non_coding_transcript_exon	Exon 1 of 1
	MT-ND5	ENST00000361567.2	TSL:6	c.-91C>A		upstream_gene	N/A	ENSP00000354813.2	P03915
	MT-ND4	ENST00000361381.2	TSL:6	c.*109C>A		downstream_gene	N/A	ENSP00000354961.2	P03905

Frequencies

Mitomap GenBank AF: 0.00010 AC: 4

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

Disease(s): CIPO

Status: Reported

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.4
Hmtvar	Benign	0.10
PhyloP100		-4.6

Other links and lift over

dbSNP: rs28508189; hg19: chrM-12247;