15-101654641-T-C

Position:

• chr15-101654641-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000335968.8(TARS3):​c.2350A>G​(p.Ile784Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TARS3 ENST00000335968.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11194143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARS3	NM_152334.3	c.2350A>G	p.Ile784Val	missense_variant	19/19	ENST00000335968.8	NP_689547.2
TARS3	XM_047432142.1	c.1621A>G	p.Ile541Val	missense_variant	16/16		XP_047288098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARS3	ENST00000335968.8	c.2350A>G	p.Ile784Val	missense_variant	19/19	1	NM_152334.3	ENSP00000338093.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2023

The c.2350A>G (p.I784V) alteration is located in exon 19 (coding exon 19) of the TARSL2 gene. This alteration results from a A to G substitution at nucleotide position 2350, causing the isoleucine (I) at amino acid position 784 to be replaced by a valine (V). 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	0.063
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.93	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.26
Sift	Benign	0.50	T
Sift4G	Benign	0.52	T
Polyphen		0.035	B
Vest4		0.067
MutPred		0.45		Gain of MoRF binding (P = 0.0919);
MVP		0.69
MPC		0.058
ClinPred		0.49	T
GERP RS		5.7
Varity_R		0.11
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-102194844;