Variant 1-184051894-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_052965.4(TSEN15):c.135+4A>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,534,856 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

TSEN15
NM_052965.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.9994

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

TSEN15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN15	NM_052965.4 linkuse as main transcript	c.135+4A>T		splice_donor_region_variant, intron_variant		ENST00000645668.2	NP_443197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN15	ENST00000645668.2 linkuse as main transcript	c.135+4A>T		splice_donor_region_variant, intron_variant			NM_052965.4	ENSP00000493902	P3	Q8WW01-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000230

AC:

AN:

147574

Hom.:

AF XY:

0.000250

AC XY:

AN XY:

79998

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000410

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000630

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000363

AC:

502

AN:

1382568

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

246

AN XY:

682528

show subpopulations

Gnomad4 AFR exome

AF:

0.0000671

Gnomad4 AMR exome

AF:

0.0000553

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000841

Gnomad4 NFE exome

AF:

0.000412

Gnomad4 OTH exome

AF:

0.000297

GnomAD4 genome

AF:

0.000223

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2024

The c.135+4A>T intronic alteration consists of a A to T substitution nucleotides after coding exon 1 in the TSEN15 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.10

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over