Variant rs7218675 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207346.3(TSEN54):c.285+32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,443,256 control chromosomes in the GnomAD database, including 351,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 24369 hom., cov: 29)

Exomes 𝑓: 0.72 ( 326830 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.00

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=-0.79).

BP6

Variant 17-75517104-C-A is Benign according to our data. Variant chr17-75517104-C-A is described in ClinVar as [Benign]. Clinvar id is 160133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75517104-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.285+32C>A		intron_variant		ENST00000333213.11	NP_997229.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.285+32C>A		intron_variant		1	NM_207346.3	ENSP00000327487	P1	Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

79302

AN:

122580

Hom.:

24374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.731

Gnomad MID

AF:

0.676

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.640

GnomAD3 exomes

AF:

0.601

AC:

114087

AN:

189872

Hom.:

36194

AF XY:

0.622

AC XY:

64119

AN XY:

103024

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.451

Gnomad SAS exome

AF:

0.674

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.622

GnomAD4 exome

AF:

0.722

AC:

952874

AN:

1320614

Hom.:

326830

Cov.:

AF XY:

0.724

AC XY:

473894

AN XY:

654972

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.660

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.720

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.748

Gnomad4 OTH exome

AF:

0.688

GnomAD4 genome

AF:

0.647

AC:

79303

AN:

122642

Hom.:

24369

Cov.:

AF XY:

0.645

AC XY:

38841

AN XY:

60212

show subpopulations

Gnomad4 AFR

AF:

0.393

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.669

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.707

Gnomad4 FIN

AF:

0.731

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.647

Hom.:

14815

Bravo

AF:

0.486

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Pontocerebellar hypoplasia type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Pontocerebellar hypoplasia type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Pontocerebellar hypoplasia type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.8

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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