Variant 15-101684218-G-A 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.1507C>T(p.Pro503Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,554 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: 0.000016 ( 0 hom. )

Consequence

TARS3
NM_152334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.75

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:

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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
TARS3	NM_152334.3 linkuse as main transcript	c.1507C>T	p.Pro503Ser	missense_variant	12/19	ENST00000335968.8	NP_689547.2
TARS3	XM_047432140.1 linkuse as main transcript	c.1507C>T	p.Pro503Ser	missense_variant	12/17		XP_047288096.1
TARS3	XM_017021912.3 linkuse as main transcript	c.1507C>T	p.Pro503Ser	missense_variant	12/16		XP_016877401.1
TARS3	XM_047432142.1 linkuse as main transcript	c.778C>T	p.Pro260Ser	missense_variant	9/16		XP_047288098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARS3	ENST00000335968.8 linkuse as main transcript	c.1507C>T	p.Pro503Ser	missense_variant	12/19	1	NM_152334.3	ENSP00000338093	P1	A2RTX5-1
TARS3	ENST00000539112.5 linkuse as main transcript	c.1507C>T	p.Pro503Ser	missense_variant, NMD_transcript_variant	12/20	1		ENSP00000439899
TARS3	ENST00000615656.1 linkuse as main transcript	c.1507C>T	p.Pro503Ser	missense_variant	12/19	5		ENSP00000478827
TARS3	ENST00000558533.5 linkuse as main transcript	c.*271C>T		3_prime_UTR_variant, NMD_transcript_variant	8/14	5		ENSP00000452740

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251018

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135652

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

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

Feb 27, 2023

The c.1507C>T (p.P503S) alteration is located in exon 12 (coding exon 12) of the TARSL2 gene. This alteration results from a C to T substitution at nucleotide position 1507, causing the proline (P) at amino acid position 503 to be replaced by a serine (S). 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

0.22

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.1

D;.

REVEL

Uncertain

0.36

Sift

Benign

0.26

T;.

Sift4G

Benign

0.63

T;T

Polyphen

0.44

B;.

Vest4

0.72

MutPred

0.47

Gain of catalytic residue at P503 (P = 0.0223);Gain of catalytic residue at P503 (P = 0.0223);

MVP

0.78

MPC

0.070

ClinPred

0.42

GERP RS

5.5

Varity_R

0.22

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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