chr9-132342660-A-G

Variant names:

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.498+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,406,720 control chromosomes in the GnomAD database, including 3,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 382 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2779 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.31

Publications

5 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=-0.9).

BP6

Variant 9-132342660-A-G is Benign according to our data. Variant chr9-132342660-A-G is described in ClinVar as Benign. ClinVar VariationId is 260508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.498+30T>C		intron_variant	Intron 5 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.498+30T>C		intron_variant	Intron 5 of 25	1	NM_015046.7	ENSP00000224140.5		Q7Z333-1

Frequencies

GnomAD3 genomes

AF:

0.0590

AC:

8973

AN:

152002

Hom.:

383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.0737

Gnomad FIN

AF:

0.0501

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0444

Gnomad OTH

AF:

0.0523

GnomAD2 exomes

AF:

0.0712

AC:

17872

AN:

251000

AF XY:

0.0690

show subpopulations

Gnomad AFR exome

AF:

0.0637

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.0357

Gnomad EAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0543

GnomAD4 exome

AF:

0.0538

AC:

67441

AN:

1254600

Hom.:

2779

Cov.:

AF XY:

0.0539

AC XY:

34255

AN XY:

635022

show subpopulations

African (AFR)

AF:

0.0605

AC:

1777

AN:

29396

American (AMR)

AF:

0.0733

AC:

3261

AN:

44482

Ashkenazi Jewish (ASJ)

AF:

0.0382

AC:

949

AN:

24846

East Asian (EAS)

AF:

0.247

AC:

9525

AN:

38626

South Asian (SAS)

AF:

0.0709

AC:

5815

AN:

82036

European-Finnish (FIN)

AF:

0.0557

AC:

2961

AN:

53172

Middle Eastern (MID)

AF:

0.0480

AC:

257

AN:

5358

European-Non Finnish (NFE)

AF:

0.0433

AC:

39978

AN:

923076

Other (OTH)

AF:

0.0544

AC:

2918

AN:

53608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3406

6812

10218

13624

17030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1548

3096

4644

6192

7740

<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:

0.0590

AC:

8977

AN:

152120

Hom.:

382

Cov.:

AF XY:

0.0599

AC XY:

4459

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0628

AC:

2605

AN:

41486

American (AMR)

AF:

0.0561

AC:

856

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3472

East Asian (EAS)

AF:

0.255

AC:

1319

AN:

5164

South Asian (SAS)

AF:

0.0735

AC:

354

AN:

4816

European-Finnish (FIN)

AF:

0.0501

AC:

531

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0444

AC:

3019

AN:

68010

Other (OTH)

AF:

0.0508

AC:

107

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

431

862

1293

1724

2155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0501

Hom.:

Bravo

AF:

0.0613

Asia WGS

AF:

0.137

AC:

475

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.90

CADD

Benign

0.026

(source)

DANN

Benign

0.40

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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