chr15-101724101-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152334.3(TARS3):​c.287C>T​(p.Ala96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000826 in 1,211,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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: not found (cov: 34)
  • Exomes 𝑓: 8.3e-7 (0 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: 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=0.06965405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS3	NM_152334.3	c.287C>T	p.Ala96Val	missense_variant	Exon 1 of 19	ENST00000335968.8	NP_689547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARS3	ENST00000335968.8	c.287C>T	p.Ala96Val	missense_variant	Exon 1 of 19	1	NM_152334.3	ENSP00000338093.3
TARS3	ENST00000539112.5	n.287C>T		non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000439899.1
TARS3	ENST00000615656.1	c.287C>T	p.Ala96Val	missense_variant	Exon 1 of 19	5		ENSP00000478827.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.26e-7 AC: 1 AN: 1211156 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 585850

African (AFR) AF: 0.00 AC: 0 AN: 24320

American (AMR) AF: 0.00 AC: 0 AN: 12970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16976

East Asian (EAS) AF: 0.00 AC: 0 AN: 27662

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3574

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 991200

Other (OTH) AF: 0.00 AC: 0 AN: 49796

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		-0.070
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.18	N;.
REVEL	Benign	0.045
Sift	Benign	0.17	T;.
Sift4G	Benign	0.078	T;T
Polyphen		0.31	B;.
Vest4		0.099
MutPred		0.095		Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);
MVP		0.30
MPC		0.91
ClinPred		0.15	T
GERP RS		1.4
PromoterAI		-0.060	Neutral
Varity_R		0.031
gMVP		0.19
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 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;