9-132283232-A-T

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.6546+32T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 1,613,742 control chromosomes in the GnomAD database, including 5,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 833 hom., cov: 32)

Exomes 𝑓: 0.048 ( 5085 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.263

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 9-132283232-A-T is Benign according to our data. Variant chr9-132283232-A-T is described in ClinVar as Benign. ClinVar VariationId is 260512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.6546+32T>A		intron_variant	Intron 19 of 25	ENST00000224140.6	NP_055861.3	Q7Z333-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SETX	ENST00000224140.6 link	c.6546+32T>A	intron_variant	Intron 19 of 25	1	NM_015046.7	ENSP00000224140.5	Q7Z333-1
SETX	ENST00000474172.1 link	n.257T>A	non_coding_transcript_exon_variant	Exon 2 of 2	3
SETX	ENST00000436441.5 link	c.1272+32T>A	intron_variant	Intron 9 of 16	5		ENSP00000409143.1	X6RI79

Frequencies

GnomAD3 genomes

AF:

0.0755

AC:

11475

AN:

152066

Hom.:

831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0697

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0469

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0276

Gnomad OTH

AF:

0.0664

GnomAD2 exomes

AF:

0.0830

AC:

20863

AN:

251328

AF XY:

0.0794

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0995

Gnomad ASJ exome

AF:

0.0486

Gnomad EAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.0447

Gnomad NFE exome

AF:

0.0273

Gnomad OTH exome

AF:

0.0616

GnomAD4 exome

AF:

0.0483

AC:

70554

AN:

1461560

Hom.:

5085

Cov.:

AF XY:

0.0492

AC XY:

35765

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.129

AC:

4326

AN:

33464

American (AMR)

AF:

0.0975

AC:

4360

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0488

AC:

1276

AN:

26132

East Asian (EAS)

AF:

0.406

AC:

16131

AN:

39684

South Asian (SAS)

AF:

0.104

AC:

8991

AN:

86244

European-Finnish (FIN)

AF:

0.0450

AC:

2406

AN:

53416

Middle Eastern (MID)

AF:

0.0779

AC:

449

AN:

5766

European-Non Finnish (NFE)

AF:

0.0256

AC:

28406

AN:

1111758

Other (OTH)

AF:

0.0697

AC:

4209

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

3354

6708

10061

13415

16769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1432

2864

4296

5728

7160

<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:

0.0755

AC:

11494

AN:

152182

Hom.:

833

Cov.:

AF XY:

0.0791

AC XY:

5887

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.123

AC:

5086

AN:

41518

American (AMR)

AF:

0.0704

AC:

1077

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3470

East Asian (EAS)

AF:

0.379

AC:

1959

AN:

5170

South Asian (SAS)

AF:

0.127

AC:

610

AN:

4822

European-Finnish (FIN)

AF:

0.0469

AC:

496

AN:

10582

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0276

AC:

1880

AN:

68010

Other (OTH)

AF:

0.0700

AC:

148

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

498

996

1493

1991

2489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0248

Hom.:

Bravo

AF:

0.0816

Asia WGS

AF:

0.255

AC:

885

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.71

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.26

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)

0.060

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