Variant 15-101724101-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152334.3(TARS3):c.287C>G(p.Ala96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,363,024 control chromosomes in the GnomAD database, including 68,648 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8876 hom., cov: 34)

Exomes 𝑓: 0.29 ( 59772 hom. )

Consequence

TARS3
NM_152334.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0700

Variant links:

Genes affected

TARS3 (HGNC:24728): (threonyl-tRNA synthetase 3) Predicted to enable threonine-tRNA ligase activity. Predicted to be involved in threonyl-tRNA aminoacylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TARS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1794356E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARS3	NM_152334.3 linkuse as main transcript	c.287C>G	p.Ala96Gly	missense_variant	1/19	ENST00000335968.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TARS3	ENST00000335968.8 linkuse as main transcript	c.287C>G	p.Ala96Gly	missense_variant	1/19	1	NM_152334.3	P1	A2RTX5-1
TARS3	ENST00000539112.5 linkuse as main transcript	c.287C>G	p.Ala96Gly	missense_variant, NMD_transcript_variant	1/20	1
TARS3	ENST00000615656.1 linkuse as main transcript	c.287C>G	p.Ala96Gly	missense_variant	1/19	5

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48360

AN:

152088

Hom.:

8871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.344

GnomAD3 exomes

AF:

0.425

AC:

8145

AN:

19156

Hom.:

2000

AF XY:

0.414

AC XY:

4647

AN XY:

11238

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.837

Gnomad SAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.294

AC:

355973

AN:

1210824

Hom.:

59772

Cov.:

AF XY:

0.300

AC XY:

175629

AN XY:

585672

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.503

Gnomad4 ASJ exome

AF:

0.399

Gnomad4 EAS exome

AF:

0.846

Gnomad4 SAS exome

AF:

0.512

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.318

AC:

48382

AN:

152200

Hom.:

8876

Cov.:

AF XY:

0.329

AC XY:

24501

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.420

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.814

Gnomad4 SAS

AF:

0.538

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.292

Hom.:

856

Bravo

AF:

0.326

TwinsUK

AF:

0.251

AC:

932

ALSPAC

AF:

0.270

AC:

1039

ESP6500AA

AF:

0.155

AC:

440

ESP6500EA

AF:

0.198

AC:

1203

ExAC

AF:

0.273

AC:

23064

Asia WGS

AF:

0.622

AC:

2156

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.7

DANN

Benign

0.96

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.62

N;.

REVEL

Benign

0.050

Sift

Benign

0.16

T;.

Sift4G

Benign

0.13

T;T

Polyphen

0.0

B;.

Vest4

0.068

MPC

0.92

ClinPred

0.0091

GERP RS

1.4

Varity_R

0.039

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over