rs2296872

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 4
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
distal hereditary motor neuropathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

SETX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 95664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.5374+16C>T		intron_variant	Intron 11 of 25	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.5374+16C>T		intron_variant	Intron 11 of 25	1	NM_015046.7	ENSP00000224140.5		Q7Z333-1
SETX	ENST00000436441.5 link	c.100+16C>T		intron_variant	Intron 1 of 16	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

GnomAD2 exomes

AF:

0.247

AC:

60988

AN:

246488

AF XY:

0.247

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 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

African (AFR)

AF:

0.395

AC:

12645

AN:

32038

American (AMR)

AF:

0.193

AC:

8594

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

6484

AN:

25626

East Asian (EAS)

AF:

0.707

AC:

27783

AN:

39316

South Asian (SAS)

AF:

0.361

AC:

30559

AN:

84640

European-Finnish (FIN)

AF:

0.168

AC:

8799

AN:

52432

Middle Eastern (MID)

AF:

0.325

AC:

1753

AN:

5386

European-Non Finnish (NFE)

AF:

0.152

AC:

159889

AN:

1052920

Other (OTH)

AF:

0.229

AC:

13291

AN:

58126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

9179

18358

27537

36716

45895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6090

12180

18270

24360

30450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38115

AN:

151898

Hom.:

6086

Cov.:

AF XY:

0.256

AC XY:

19037

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.383

AC:

15854

AN:

41370

American (AMR)

AF:

0.191

AC:

2922

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

922

AN:

3468

East Asian (EAS)

AF:

0.671

AC:

3476

AN:

5182

South Asian (SAS)

AF:

0.379

AC:

1824

AN:

4810

European-Finnish (FIN)

AF:

0.168

AC:

1775

AN:

10536

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.157

AC:

10642

AN:

67956

Other (OTH)

AF:

0.229

AC:

483

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1312

2623

3935

5246

6558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.212

Hom.:

772

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 14, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amyotrophic lateral sclerosis type 4

Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.12

(source)

DANN

Benign

0.55

PhyloP100

-1.8

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over