5-33453263-CT-C

Variant names:

• chr5-33453263-CT-C
• rs35931457
• NM_152295.5:c.330-4delT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_152295.5(TARS1):​c.330-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 105,184 control chromosomes in the GnomAD database, including 1,223 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (1223 hom., cov: 22)
  • Exomes 𝑓: 0.30 (124 hom.)
  • Failed GnomAD Quality Control
• Consequence: TARS1 NM_152295.5 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.694

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 -9 ACMG points.

• BP6: Variant 5-33453263-CT-C is Benign according to our data. Variant chr5-33453263-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3060916.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS1	NM_152295.5	c.330-4delT		splice_region_variant, intron_variant	Intron 3 of 18	ENST00000265112.8	NP_689508.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARS1	ENST00000265112.8	c.330-25delT		intron_variant	Intron 3 of 18	1	NM_152295.5	ENSP00000265112.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 18920 AN: 105182 Hom.: 1221 Cov.: 22

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.164

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.304 AC: 358596 AN: 1178478 Hom.: 124 Cov.: 0 AF XY: 0.299 AC XY: 173477 AN XY: 579342

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.180 AC: 18909 AN: 105184 Hom.: 1223 Cov.: 22 AF XY: 0.179 AC XY: 8877 AN XY: 49628

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0454

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TARS1-related disorder Benign:1

Oct 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35931457; hg19: chr5-33453368;