rs8074291

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_207346.3(TSEN54):c.285+3G>A 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 0.139 in 1,592,506 control chromosomes in the GnomAD database, including 17,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3402 hom., cov: 33)

Exomes 𝑓: 0.13 ( 14270 hom. )

Consequence

TSEN54
NM_207346.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.001151

Clinical Significance

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

Conservation

PhyloP100: 2.36

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 17-75517075-G-A is Benign according to our data. Variant chr17-75517075-G-A is described in ClinVar as [Benign]. Clinvar id is 137755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75517075-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN54	NM_207346.3 linkuse as main transcript	c.285+3G>A		splice_donor_region_variant, intron_variant		ENST00000333213.11

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28151

AN:

152100

Hom.:

3392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0207

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.129

AC:

27006

AN:

209186

Hom.:

2113

AF XY:

0.127

AC XY:

14427

AN XY:

113862

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.0874

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.0181

Gnomad SAS exome

AF:

0.0976

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.134

AC:

193417

AN:

1440288

Hom.:

14270

Cov.:

AF XY:

0.133

AC XY:

94938

AN XY:

714632

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.0900

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.0181

Gnomad4 SAS exome

AF:

0.0989

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.185

AC:

28198

AN:

152218

Hom.:

3402

Cov.:

AF XY:

0.181

AC XY:

13502

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.0203

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.153

Hom.:

894

Bravo

AF:

0.192

Asia WGS

AF:

0.0890

AC:

313

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Pontoneocerebellar hypoplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.010

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