chrM-12297-T-C

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

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-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
	MT-ND4	ENST00000361381.2	TSL:6	c.*160T>C		downstream_gene	N/A	ENSP00000354961.2

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

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiomyopathy, mitochondrial Pathogenic:1

Apr 01, 2001

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.12297T>C variant in MT-TL2 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2

not provided Other:1

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpretted as Uncertain significance and reported on 04/12/2017 by GTR ID MNG Laboratories. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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;