M-12280-A-G

Position:

• chrM-12280-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0016 (AC: 95)
• Consequence: TRNL2 stop_retained
• Scores: Mitotip Benign 3.0
• Clinical Significance: Benign criteria provided, single submitter B:1 Hypertension
• Conservation: PhyloP100: 0.219

Genes affected

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

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-12280-A-G is Benign according to our data. Variant chrM-12280-A-G is described in ClinVar as [Benign]. Clinvar id is 690185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNL2	unassigned_transcript_4814	c.15A>G	p.Ter5Ter	stop_retained_variant	1/1
TRNS2	unassigned_transcript_4813	c.*15A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0016 AC: 95

Gnomad homoplasmic AF: 0.0015 AC: 83 AN: 56418

Gnomad heteroplasmic AF: 0.00021 AC: 12 AN: 56418

Mitomap

Hypertension

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome 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.12280A>G variant in MT-TL2 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	3.0
Hmtvar	Benign	0.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603223649; hg19: chrM-12281;