Variant rs56895494 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.370-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,605,770 control chromosomes in the GnomAD database, including 13,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1141 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12357 hom. )

Consequence

TSEN54
NM_207346.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0230

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:

TSEN54 (HGNC:):

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=-0.7).

BP6

Variant 17-75517538-C-A is Benign according to our data. Variant chr17-75517538-C-A is described in ClinVar as [Benign]. Clinvar id is 137757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75517538-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 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.370-19C>A		intron_variant		ENST00000333213.11	NP_997229.2	Q7Z6J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11 linkuse as main transcript	c.370-19C>A		intron_variant		1	NM_207346.3	ENSP00000327487.6		Q7Z6J9-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18206

AN:

152002

Hom.:

1140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.115

AC:

28915

AN:

250960

Hom.:

1888

AF XY:

0.117

AC XY:

15843

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0715

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0182

Gnomad SAS exome

AF:

0.0990

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.127

AC:

185288

AN:

1453650

Hom.:

12357

Cov.:

AF XY:

0.127

AC XY:

91932

AN XY:

723670

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.0723

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0181

Gnomad4 SAS exome

AF:

0.0989

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.120

AC:

18220

AN:

152120

Hom.:

1141

Cov.:

AF XY:

0.118

AC XY:

8763

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.0201

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.135

Hom.:

265

Bravo

AF:

0.117

Asia WGS

AF:

0.0740

AC:

260

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 31, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.2

DANN

Benign

0.77

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