Genetic Variant TARS1:c.330-7_330-4dupTTTT (chr5-33453263-C-CTTTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_152295.5(TARS1):c.330-7_330-4dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,342,408 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000060 ( 1 hom. )

Consequence

TARS1
NM_152295.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.694

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS1	NM_152295.5 link	c.330-7_330-4dupTTTT		splice_region_variant, intron_variant	Intron 3 of 18	ENST00000265112.8	NP_689508.3	P26639-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARS1	ENST00000265112.8 link	c.330-26_330-25insTTTT		intron_variant	Intron 3 of 18	1	NM_152295.5	ENSP00000265112.3		P26639-1

Frequencies

GnomAD3 genomes

AF:

0.0000190

AC:

AN:

105220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000222

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000197

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000598

AC:

AN:

1237186

Hom.:

Cov.:

AF XY:

0.0000560

AC XY:

AN XY:

607428

show subpopulations

Gnomad4 AFR exome

AF:

0.0000742

Gnomad4 AMR exome

AF:

0.0000479

Gnomad4 ASJ exome

AF:

0.0000511

Gnomad4 EAS exome

AF:

0.000154

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000854

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.0000792

GnomAD4 genome

AF:

0.0000190

AC:

AN:

105222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49656

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000222

Gnomad4 NFE

AF:

0.0000197

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

5-33453263-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over