rs121434463

chrM-12320-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000387456.1(MT-TL2):n.55A>G variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TL2 ENST00000387456.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 11
• Clinical Significance: Pathogenic no assertion criteria provided P:1 MM
• Conservation: PhyloP100: 6.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-12320-A-G is Pathogenic according to our data. Variant chrM-12320-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 9587.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNL2	TRNL2.1	n.55A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TL2	ENST00000387456.1	n.55A>G		non_coding_transcript_exon_variant	1/1
MT-ND5	ENST00000361567.2			upstream_gene_variant				P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

MM

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Inborn mitochondrial myopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 1997

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Pathogenic	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434463; hg19: chrM-12321;