9-132297025-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015046.7(SETX):c.5811T>C(p.Asp1937Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,612,012 control chromosomes in the GnomAD database, including 51,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 11023 hom., cov: 32)

Exomes 𝑓: 0.20 ( 40460 hom. )

Consequence

SETX
NM_015046.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 0.690

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 9-132297025-A-G is Benign according to our data. Variant chr9-132297025-A-G is described in ClinVar as [Benign]. Clinvar id is 95667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132297025-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.69 with no splicing effect.

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 rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.5811T>C	p.Asp1937Asp	synonymous_variant	Exon 14 of 26	ENST00000224140.6	NP_055861.3	Q7Z333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETX	ENST00000224140.6 link	c.5811T>C	p.Asp1937Asp	synonymous_variant	Exon 14 of 26	1	NM_015046.7	ENSP00000224140.5		Q7Z333-1
SETX	ENST00000436441.5 link	c.537T>C	p.Asp179Asp	synonymous_variant	Exon 4 of 17	5		ENSP00000409143.1		X6RI79

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48155

AN:

151882

Hom.:

10981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.265

AC:

66348

AN:

249954

Hom.:

12526

AF XY:

0.260

AC XY:

35190

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.364

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.199

AC:

290173

AN:

1460014

Hom.:

40460

Cov.:

AF XY:

0.202

AC XY:

147009

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.632

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.253

Gnomad4 EAS exome

AF:

0.706

Gnomad4 SAS exome

AF:

0.362

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.317

AC:

48251

AN:

151998

Hom.:

11023

Cov.:

AF XY:

0.320

AC XY:

23733

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.616

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.670

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.221

Hom.:

3899

Bravo

AF:

0.335

Asia WGS

AF:

0.503

AC:

1750

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:10

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 14, 2012	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 12, 2017	- -

Amyotrophic lateral sclerosis type 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -
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. -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -
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. -

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 04, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.0

DANN

Benign

0.46

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