M-12235-T-C

Position:

• chrM-12235-T-C

Variant summary

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

The ENST00000387449.1(MT-TS2):​n.29T>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 0.0038 (AC: 230)
• Consequence: MT-TS2 ENST00000387449.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 9.0
• Clinical Significance: Benign criteria provided, single submitter B:1 Hearing-loss-patient
• Conservation: PhyloP100: 0.152

Genes affected

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

TRNS2 (HGNC:):

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

MT-TH (HGNC:7487): (mitochondrially encoded tRNA histidine)

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-12235-T-C is Benign according to our data. Variant chrM-12235-T-C is described in ClinVar as [Benign]. Clinvar id is 690167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 29

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNS2	TRNS2.1	n.29T>C		non_coding_transcript_exon_variant	1/1
TRNL2	TRNL2.1			upstream_gene_variant
TRNH	TRNH.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TS2	ENST00000387449.1	n.29T>C		non_coding_transcript_exon_variant	1/1
MT-TL2	ENST00000387456.1			upstream_gene_variant
MT-TH	ENST00000387441.1			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: 0.0038 AC: 230

Gnomad homoplasmic AF: 0.00051 AC: 29 AN: 56428

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56428

Mitomap

Hearing-loss-patient

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.12235T>C variant in MT-TS2 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	9.0
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: rs1556424083; hg19: chrM-12236;