Variant 15-101654611-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152334.3(TARS3):c.2380C>G(p.Arg794Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TARS3
NM_152334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARS3	NM_152334.3 linkuse as main transcript	c.2380C>G	p.Arg794Gly	missense_variant	19/19	ENST00000335968.8	NP_689547.2
TARS3	XM_047432142.1 linkuse as main transcript	c.1651C>G	p.Arg551Gly	missense_variant	16/16		XP_047288098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARS3	ENST00000335968.8 linkuse as main transcript	c.2380C>G	p.Arg794Gly	missense_variant	19/19	1	NM_152334.3	ENSP00000338093	P1	A2RTX5-1
TARS3	ENST00000539112.5 linkuse as main transcript	c.*233C>G		3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000439899
TARS3	ENST00000559492.1 linkuse as main transcript	n.613C>G		non_coding_transcript_exon_variant	4/4	5
TARS3	ENST00000558533.5 linkuse as main transcript	c.*1071C>G		3_prime_UTR_variant, NMD_transcript_variant	14/14	5		ENSP00000452740

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251266

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.2380C>G (p.R794G) alteration is located in exon 19 (coding exon 19) of the TARSL2 gene. This alteration results from a C to G substitution at nucleotide position 2380, causing the arginine (R) at amino acid position 794 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.64

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.70

Vest4

0.41

MutPred

0.58

Loss of MoRF binding (P = 0.045);

MVP

0.60

MPC

0.29

ClinPred

0.98

GERP RS

5.7

Varity_R

0.73

gMVP

0.70

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over