Variant 17-75516991-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_207346.3(TSEN54):c.222-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,570,044 control chromosomes in the GnomAD database, including 777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 67 hom., cov: 33)

Exomes 𝑓: 0.029 ( 710 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.392

Variant links:

Genes affected

TSEN54 (HGNC:27561): (tRNA splicing endonuclease subunit 54) This gene encodes a subunit of the tRNA splicing endonuclease complex, which catalyzes the removal of introns from precursor tRNAs. The complex is also implicated in pre-mRNA 3-prime end processing. Mutations in this gene result in pontocerebellar hypoplasia type 2.[provided by RefSeq, Oct 2009]

TSEN54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-75516991-C-T is Benign according to our data. Variant chr17-75516991-C-T is described in ClinVar as [Benign]. Clinvar id is 263291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75516991-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0231 (3517/152308) while in subpopulation SAS AF= 0.0396 (191/4826). AF 95% confidence interval is 0.035. There are 67 homozygotes in gnomad4. There are 1705 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.222-18C>T		intron_variant		ENST00000333213.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.222-18C>T		intron_variant		1	NM_207346.3	P1	Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3517

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00548

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0398

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0318

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0273

AC:

4871

AN:

178474

Hom.:

AF XY:

0.0288

AC XY:

2774

AN XY:

96250

show subpopulations

Gnomad AFR exome

AF:

0.00376

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0564

Gnomad EAS exome

AF:

0.000148

Gnomad SAS exome

AF:

0.0380

Gnomad FIN exome

AF:

0.0335

Gnomad NFE exome

AF:

0.0315

Gnomad OTH exome

AF:

0.0327

GnomAD4 exome

AF:

0.0286

AC:

40552

AN:

1417736

Hom.:

710

Cov.:

AF XY:

0.0292

AC XY:

20482

AN XY:

701256

show subpopulations

Gnomad4 AFR exome

AF:

0.00395

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0533

Gnomad4 EAS exome

AF:

0.0000537

Gnomad4 SAS exome

AF:

0.0373

Gnomad4 FIN exome

AF:

0.0322

Gnomad4 NFE exome

AF:

0.0293

Gnomad4 OTH exome

AF:

0.0279

GnomAD4 genome

AF:

0.0231

AC:

3517

AN:

152308

Hom.:

Cov.:

AF XY:

0.0229

AC XY:

1705

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00546

Gnomad4 AMR

AF:

0.0219

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0396

Gnomad4 FIN

AF:

0.0333

Gnomad4 NFE

AF:

0.0318

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0327

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.6

DANN

Benign

0.90

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

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