5-33453263-CTT-C

Position:

• chr5-33453263-CTT-C

Variant summary

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

The NM_152295.5(TARS1):​c.330-5_330-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,240,962 control chromosomes in the GnomAD database, including 17 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 0.0014 (0 hom., cov: 22)
  • Exomes 𝑓: 0.095 (17 hom.)
• 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]

TARS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 5-33453263-CTT-C is Benign according to our data. Variant chr5-33453263-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055549.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARS1	NM_152295.5	c.330-5_330-4delTT		splice_region_variant, intron_variant		ENST00000265112.8	NP_689508.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARS1	ENST00000265112.8	c.330-5_330-4delTT		splice_region_variant, intron_variant		1	NM_152295.5	ENSP00000265112.3

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 143 AN: 105202 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000840

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00266

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00216

GnomAD4 exome AF: 0.0945 AC: 107352 AN: 1135758 Hom.: 17 AF XY: 0.0964 AC XY: 53815 AN XY: 558080

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0905

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.00136 AC: 143 AN: 105204 Hom.: 0 Cov.: 22 AF XY: 0.00153 AC XY: 76 AN XY: 49646

Gnomad4 AFR AF: 0.00349

Gnomad4 AMR AF: 0.000840

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00137

Gnomad4 FIN AF: 0.00266

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00215

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TARS1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2020

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)		0.0		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: rs35931457; hg19: chr5-33453368;