1-150487872-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025150.5(TARS2):c.81C>T(p.Thr27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,612,718 control chromosomes in the GnomAD database, including 1,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 432 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1313 hom. )

Consequence

TARS2
NM_025150.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.337

Variant links:

Genes affected

TARS2 (HGNC:30740): (threonyl-tRNA synthetase 2, mitochondrial) This gene encodes a member of the class-II aminoacyl-tRNA synthetase family. The encoded protein is a mitochondrial aminoacyl-tRNA synthetase. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 4. [provided by RefSeq, Dec 2012]

TARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-150487872-C-T is Benign according to our data. Variant chr1-150487872-C-T is described in ClinVar as [Benign]. Clinvar id is 380568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.337 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARS2	NM_025150.5 linkuse as main transcript	c.81C>T	p.Thr27=	synonymous_variant	2/18	ENST00000369064.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TARS2	ENST00000369064.8 linkuse as main transcript	c.81C>T	p.Thr27=	synonymous_variant	2/18	1	NM_025150.5	P1	Q9BW92-1

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7201

AN:

152044

Hom.:

428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0824

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.0607

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0386

AC:

9686

AN:

250824

Hom.:

840

AF XY:

0.0299

AC XY:

4060

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.00787

Gnomad EAS exome

AF:

0.0508

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000794

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0120

AC:

17455

AN:

1460556

Hom.:

1313

Cov.:

AF XY:

0.0106

AC XY:

7719

AN XY:

726586

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.00728

Gnomad4 EAS exome

AF:

0.0949

Gnomad4 SAS exome

AF:

0.00356

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000544

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0474

AC:

7218

AN:

152162

Hom.:

432

Cov.:

AF XY:

0.0480

AC XY:

3568

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.0604

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0190

Hom.:

120

Bravo

AF:

0.0609

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

EpiCase

AF:

0.000982

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 16, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

TARS2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 22, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over