rs7705177

Positions:

• chr5-33446950-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152295.5(TARS1):​c.138+1546C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,942 control chromosomes in the GnomAD database, including 5,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (5065 hom., cov: 32)
• Consequence: TARS1 NM_152295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARS1	NM_152295.5	c.138+1546C>T		intron_variant		ENST00000265112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TARS1	ENST00000265112.8	c.138+1546C>T		intron_variant		1	NM_152295.5	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33896 AN: 151824 Hom.: 5055 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33935 AN: 151942 Hom.: 5065 Cov.: 32 AF XY: 0.222 AC XY: 16475 AN XY: 74268

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0275

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.193

Alfa AF: 0.201 Hom.: 626

Bravo AF: 0.226

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs7705177; hg19: chr5-33447056;