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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNL2	unassigned_transcript_4814	c.32T>C	p.Leu11Pro	missense_variant	Exon 1 of 1
ND5	unassigned_transcript_4815	c.-40T>C		upstream_gene_variant
ND4	unassigned_transcript_4811	c.*160T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND5	ENST00000361567.2	c.-40T>C		upstream_gene_variant		6		ENSP00000354813.2
MT-ND4	ENST00000361381.2	c.*160T>C		downstream_gene_variant		6		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 v4.3

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;