chr5-33453371-A-T

Variant names:

• chr5-33453371-A-T
• NM_152295.5:c.412A>T

Variant summary

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

The NM_152295.5(TARS1):​c.412A>T​(p.Thr138Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TARS1 NM_152295.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.37

Genes affected

TARS1 (HGNC:11572): (threonyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Threonyl-tRNA synthetase belongs to the class-II aminoacyl-tRNA synthetase family [provided by RefSeq, Jul 2008]

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=0.15288705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS1	NM_152295.5	c.412A>T	p.Thr138Ser	missense_variant	Exon 4 of 19	ENST00000265112.8	NP_689508.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARS1	ENST00000265112.8	c.412A>T	p.Thr138Ser	missense_variant	Exon 4 of 19	1	NM_152295.5	ENSP00000265112.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.54	.;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.14	N;N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.23	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.30
MutPred		0.40		Gain of disorder (P = 0.0768);Gain of disorder (P = 0.0768);.;
MVP		0.51
MPC		0.18
ClinPred		0.19	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.045
gMVP		0.14

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: chr5-33453476;