chr9-132275447-A-C

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.6936-27T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,576,564 control chromosomes in the GnomAD database, including 1,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 142 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1338 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

Publications

2 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=-0.83).

BP6

Variant 9-132275447-A-C is Benign according to our data. Variant chr9-132275447-A-C is described in ClinVar as Benign. ClinVar VariationId is 260515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.6936-27T>G		intron_variant	Intron 22 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.6936-27T>G	intron_variant	Intron 22 of 25	1	NM_015046.7	ENSP00000224140.5	Q7Z333-1
SETX	ENST00000436441.5 link	c.1662-27T>G	intron_variant	Intron 12 of 16	5		ENSP00000409143.1	X6RI79
SETX	ENST00000464133.1 link	n.134-27T>G	intron_variant	Intron 2 of 2	2
SETX	ENST00000477049.1 link	n.-65T>G	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3740

AN:

152168

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00487

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.0673

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0240

Gnomad OTH

AF:

0.0296

GnomAD2 exomes

AF:

0.0378

AC:

8888

AN:

235298

AF XY:

0.0393

show subpopulations

Gnomad AFR exome

AF:

0.00438

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0249

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0294

AC:

41806

AN:

1424282

Hom.:

1338

Cov.:

AF XY:

0.0304

AC XY:

21560

AN XY:

709606

show subpopulations

African (AFR)

AF:

0.00421

AC:

138

AN:

32788

American (AMR)

AF:

0.0133

AC:

578

AN:

43436

Ashkenazi Jewish (ASJ)

AF:

0.0470

AC:

1212

AN:

25812

East Asian (EAS)

AF:

0.189

AC:

7450

AN:

39320

South Asian (SAS)

AF:

0.0573

AC:

4852

AN:

84636

European-Finnish (FIN)

AF:

0.0129

AC:

650

AN:

50472

Middle Eastern (MID)

AF:

0.0644

AC:

350

AN:

5434

European-Non Finnish (NFE)

AF:

0.0224

AC:

24236

AN:

1083314

Other (OTH)

AF:

0.0396

AC:

2340

AN:

59070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

1674

3347

5021

6694

8368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1014

2028

3042

4056

5070

<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:

0.0245

AC:

3729

AN:

152282

Hom.:

142

Cov.:

AF XY:

0.0249

AC XY:

1853

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00486

AC:

202

AN:

41556

American (AMR)

AF:

0.0164

AC:

251

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0513

AC:

178

AN:

3472

East Asian (EAS)

AF:

0.177

AC:

918

AN:

5174

South Asian (SAS)

AF:

0.0670

AC:

323

AN:

4824

European-Finnish (FIN)

AF:

0.0118

AC:

125

AN:

10624

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0240

AC:

1635

AN:

68020

Other (OTH)

AF:

0.0298

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0263

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.120

AC:

416

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

Aug 17, 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

-0.83

CADD

Benign

6.7

(source)

DANN

Benign

0.81

PhyloP100

1.0

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