rs3831154

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_015046.7(SETX):c.5781+12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,582,696 control chromosomes in the GnomAD database, including 41,346 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6056 hom., cov: 26)

Exomes 𝑓: 0.19 ( 35290 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0720

Publications

3 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 -16 ACMG points.

BP6

Variant 9-132298067-C-CA is Benign according to our data. Variant chr9-132298067-C-CA is described in ClinVar as Benign. ClinVar VariationId is 95666.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.5781+12dupT		intron_variant	Intron 13 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.5781+12_5781+13insT		intron_variant	Intron 13 of 25	1	NM_015046.7	ENSP00000224140.5		Q7Z333-1
SETX	ENST00000436441.5 link	c.507+12_507+13insT		intron_variant	Intron 3 of 16	5		ENSP00000409143.1		X6RI79

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37990

AN:

151828

Hom.:

6044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.228

GnomAD2 exomes

AF:

0.248

AC:

62201

AN:

251208

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.192

AC:

274300

AN:

1430748

Hom.:

35290

Cov.:

AF XY:

0.196

AC XY:

140165

AN XY:

713828

show subpopulations

African (AFR)

AF:

0.392

AC:

12840

AN:

32758

American (AMR)

AF:

0.193

AC:

8616

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

6557

AN:

25926

East Asian (EAS)

AF:

0.706

AC:

27875

AN:

39500

South Asian (SAS)

AF:

0.361

AC:

30858

AN:

85566

European-Finnish (FIN)

AF:

0.169

AC:

8991

AN:

53358

Middle Eastern (MID)

AF:

0.328

AC:

1871

AN:

5702

European-Non Finnish (NFE)

AF:

0.151

AC:

163160

AN:

1083990

Other (OTH)

AF:

0.228

AC:

13532

AN:

59270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

9694

19388

29082

38776

48470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6260

12520

18780

25040

31300

<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:

0.250

AC:

38040

AN:

151948

Hom.:

6056

Cov.:

AF XY:

0.256

AC XY:

19006

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.382

AC:

15799

AN:

41378

American (AMR)

AF:

0.192

AC:

2925

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

919

AN:

3462

East Asian (EAS)

AF:

0.670

AC:

3458

AN:

5158

South Asian (SAS)

AF:

0.379

AC:

1825

AN:

4818

European-Finnish (FIN)

AF:

0.169

AC:

1784

AN:

10560

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10630

AN:

67994

Other (OTH)

AF:

0.230

AC:

485

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1346

2692

4037

5383

6729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.199

Hom.:

785

Bravo

AF:

0.258

Asia WGS

AF:

0.490

AC:

1704

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 14, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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;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

- -

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 27, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.072

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