rs121434464

Variant names:

• chrM-12297-T-C
• rs121434464
• unassigned_transcript_4814:c.32T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNL2):​c.32T>C​(p.Leu11Pro) variant causes a missense change. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00080 (AC: 50)
• Consequence: TRNL2 ENST00000000000 missense
• Scores: Mitotip Uncertain 12
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 O:1 Dilated-Cardiomyopathy-/-Leigh-Syndrome-/-Failure-to-Thrive-&-LA
• Conservation: PhyloP100: 4.68
• Publications: 2 publications found

Genes affected

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

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]

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 -6 ACMG points.

• BP6: Variant M-12297-T-C is Benign according to our data. Variant chrM-12297-T-C is described in ClinVar as Benign. ClinVar VariationId is 9588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 90

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387456.1. 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-TL2	ENST00000387456.1	TSL:6	n.32T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-ND5	ENST00000361567.2	TSL:6	c.-40T>C		upstream_gene	N/A	ENSP00000354813.2	P03915
	MT-ND4	ENST00000361381.2	TSL:6	c.*160T>C		downstream_gene	N/A	ENSP00000354961.2	P03905

Frequencies

Mitomap GenBank AF: 0.00080 AC: 50

Gnomad homoplasmic AF: 0.0016 AC: 90 AN: 56423

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56423

Alfa AF: 0.000628 Hom.: 14

Mitomap

Disease(s): Dilated-Cardiomyopathy-/-Leigh-Syndrome-/-Failure-to-Thrive-&-LA

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Cardiomyopathy, mitochondrial (1)
-	-	1	MELAS syndrome (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	12
Hmtvar	Pathogenic	0.55
PhyloP100		4.7

Other links and lift over

dbSNP: rs121434464; hg19: chrM-12298;