chrM-12311-T-C

Position:

• chrM-12311-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000387456.1(MT-TL2):​n.46T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0012 (AC: 74)
• Consequence: MT-TL2 ENST00000387456.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 10
• Clinical Significance: Benign criteria provided, single submitter B:1 CPEO
• Conservation: PhyloP100: 0.115

Genes affected

MT-TL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNL2 (HGNC:):

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-TS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-12311-T-C is Benign according to our data. Variant chrM-12311-T-C is described in ClinVar as [Benign]. Clinvar id is 690195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNL2	TRNL2.1	n.46T>C		non_coding_transcript_exon_variant	1/1
TRNS2	TRNS2.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TL2	ENST00000387456.1	n.46T>C		non_coding_transcript_exon_variant	1/1
MT-ND5	ENST00000361567.2			upstream_gene_variant				P1
MT-TS2	ENST00000387449.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0012 AC: 74

Gnomad homoplasmic AF: 0.0015 AC: 85 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Mitomap

CPEO

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jul 12, 2019

The NC_012920.1:m.12311T>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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	10
Hmtvar	Benign	0.050

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201754056; hg19: chrM-12312;