Variant rs2296872 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_015046.7(SETX):c.5374+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,546,828 control chromosomes in the GnomAD database, including 40,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6086 hom., cov: 32)

Exomes 𝑓: 0.19 ( 34827 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.83

Variant links:

Genes affected

SETX (HGNC:445): (senataxin) This gene encodes a protein named for its homology to the Sen1p protein of fungi which has RNA helicase activity encoded by a domain at the C-terminal end of the protein. The protein encoded by this gene contains a DNA/RNA helicase domain at its C-terminal end which suggests that it may be involved in both DNA and RNA processing. Mutations in this gene have been associated with ataxia-ocular apraxia-2 (AOA2) and an autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS4). [provided by RefSeq, Jul 2008]

SETX 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=-0.96).

BP6

Variant 9-132311741-G-A is Benign according to our data. Variant chr9-132311741-G-A is described in ClinVar as [Benign]. Clinvar id is 95664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132311741-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.5374+16C>T		intron_variant		ENST00000224140.6	NP_055861.3	Q7Z333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETX	ENST00000224140.6 link	c.5374+16C>T		intron_variant		1	NM_015046.7	ENSP00000224140.5		Q7Z333-1
SETX	ENST00000436441.5 link	c.100+16C>T		intron_variant		5		ENSP00000409143.1		X6RI79

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38068

AN:

151780

Hom.:

6076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.247

AC:

60988

AN:

246488

Hom.:

10267

AF XY:

0.247

AC XY:

32996

AN XY:

133450

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.193

AC:

269797

AN:

1394930

Hom.:

34827

Cov.:

AF XY:

0.198

AC XY:

138087

AN XY:

697938

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.253

Gnomad4 EAS exome

AF:

0.707

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.251

AC:

38115

AN:

151898

Hom.:

6086

Cov.:

AF XY:

0.256

AC XY:

19037

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.671

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.207

Hom.:

718

Bravo

AF:

0.259

Asia WGS

AF:

0.491

AC:

1706

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 14, 2012	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Jul 03, 2018	- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Amyotrophic lateral sclerosis type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.12

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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