15-101724101-G-C

Variant names:

• chr15-101724101-G-C
• rs1143138
• NM_152334.3:c.287C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A96D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.32 (8876 hom., cov: 34)
  • Exomes 𝑓: 0.29 (59772 hom.)
• Consequence: TARS3 NM_152334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARS3	NM_152334.3	MANE Select	c.287C>G	p.Ala96Gly	missense	Exon 1 of 19	NP_689547.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARS3	ENST00000335968.8	TSL:1 MANE Select	c.287C>G	p.Ala96Gly	missense	Exon 1 of 19	ENSP00000338093.3	A2RTX5-1
	TARS3	ENST00000539112.5	TSL:1	n.287C>G		non_coding_transcript_exon	Exon 1 of 20	ENSP00000439899.1	B7ZLP8
	TARS3	ENST00000947773.1		c.287C>G	p.Ala96Gly	missense	Exon 1 of 20	ENSP00000617832.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48360 AN: 152088 Hom.: 8871 Cov.: 34

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

GnomAD2 exomes AF: 0.425 AC: 8145 AN: 19156 AF XY: 0.414

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 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.: 34 AF XY: 0.300 AC XY: 175629 AN XY: 585672

African (AFR) AF: 0.251 AC: 6112 AN: 24318

American (AMR) AF: 0.503 AC: 6511 AN: 12950

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 6764 AN: 16970

East Asian (EAS) AF: 0.846 AC: 23395 AN: 27662

South Asian (SAS) AF: 0.512 AC: 27552 AN: 53804

European-Finnish (FIN) AF: 0.311 AC: 9564 AN: 30788

Middle Eastern (MID) AF: 0.439 AC: 1567 AN: 3568

European-Non Finnish (NFE) AF: 0.260 AC: 257634 AN: 990976

Other (OTH) AF: 0.339 AC: 16874 AN: 49788

GnomAD4 genome AF: 0.318 AC: 48382 AN: 152200 Hom.: 8876 Cov.: 34 AF XY: 0.329 AC XY: 24501 AN XY: 74412

African (AFR) AF: 0.255 AC: 10588 AN: 41548

American (AMR) AF: 0.420 AC: 6423 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.814 AC: 4202 AN: 5164

South Asian (SAS) AF: 0.538 AC: 2597 AN: 4830

European-Finnish (FIN) AF: 0.321 AC: 3400 AN: 10608

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.274 AC: 18657 AN: 67970

Other (OTH) AF: 0.342 AC: 723 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.56	T
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	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.070
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.050
Sift	Benign	0.16	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.068
MPC		0.92
ClinPred		0.0091	T
GERP RS		1.4
PromoterAI		-0.069	Neutral
Varity_R		0.039
gMVP		0.14
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1143138; hg19: chr15-102264304; COSMIC: COSV60108078; COSMIC: COSV60108078;