Genetic Variant TARS3:p.Ala96Asp (chr15-101724101-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152334.3(TARS3):c.287C>A(p.Ala96Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,211,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

TARS3
NM_152334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0700

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07910949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS3	NM_152334.3 link	c.287C>A	p.Ala96Asp	missense_variant	Exon 1 of 19	ENST00000335968.8	NP_689547.2	A2RTX5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TARS3	ENST00000335968.8 link	c.287C>A	p.Ala96Asp	missense_variant	Exon 1 of 19	1	NM_152334.3	ENSP00000338093.3	A2RTX5-1
TARS3	ENST00000539112.5 link	n.287C>A		non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000439899.1	B7ZLP8
TARS3	ENST00000615656.1 link	c.287C>A	p.Ala96Asp	missense_variant	Exon 1 of 19	5		ENSP00000478827.1	B7ZLP8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000578

AC:

AN:

1211156

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

585850

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24320

American (AMR)

AF:

0.00

AC:

AN:

12970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16976

East Asian (EAS)

AF:

0.00

AC:

AN:

27662

South Asian (SAS)

AF:

0.00

AC:

AN:

53850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3574

European-Non Finnish (NFE)

AF:

0.00000706

AC:

AN:

991200

Other (OTH)

AF:

0.00

AC:

AN:

49796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.287C>A (p.A96D) alteration is located in exon 1 (coding exon 1) of the TARSL2 gene. This alteration results from a C to A substitution at nucleotide position 287, causing the alanine (A) at amino acid position 96 to be replaced by an aspartic acid (D). 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

0.099

BayesDel_addAF

Benign

-0.0049

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;.

PhyloP100

-0.070

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.62

N;.

REVEL

Benign

0.055

Sift

Benign

0.046

D;.

Sift4G

Benign

0.14

T;T

Polyphen

0.099

B;.

Vest4

0.14

MutPred

0.20

Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);

MVP

0.33

MPC

1.4

ClinPred

0.15

GERP RS

1.4

PromoterAI

-0.069

Neutral

(source)

Varity_R

0.12

gMVP

0.29

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over