9-132278281-C-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.6655-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,611,106 control chromosomes in the GnomAD database, including 102,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17939 hom., cov: 30)

Exomes 𝑓: 0.32 ( 84594 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.881

Publications

15 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=-0.91).

BP6

Variant 9-132278281-C-T is Benign according to our data. Variant chr9-132278281-C-T is described in ClinVar as [Benign]. Clinvar id is 260513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.6655-24G>A		intron_variant	Intron 20 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.6655-24G>A	intron_variant	Intron 20 of 25	1	NM_015046.7	ENSP00000224140.5	Q7Z333-1
SETX	ENST00000436441.5 link	c.1381-24G>A	intron_variant	Intron 10 of 16	5		ENSP00000409143.1	X6RI79
SETX	ENST00000464133.1 link	n.-172G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67058

AN:

151646

Hom.:

17894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.416

GnomAD2 exomes

AF:

0.378

AC:

94805

AN:

251016

AF XY:

0.374

show subpopulations

Gnomad AFR exome

AF:

0.755

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.321

AC:

469136

AN:

1459342

Hom.:

84594

Cov.:

AF XY:

0.325

AC XY:

235758

AN XY:

726154

show subpopulations

African (AFR)

AF:

0.762

AC:

25490

AN:

33460

American (AMR)

AF:

0.295

AC:

13185

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

10268

AN:

26116

East Asian (EAS)

AF:

0.723

AC:

28701

AN:

39684

South Asian (SAS)

AF:

0.436

AC:

37622

AN:

86202

European-Finnish (FIN)

AF:

0.300

AC:

15997

AN:

53372

Middle Eastern (MID)

AF:

0.507

AC:

2919

AN:

5756

European-Non Finnish (NFE)

AF:

0.282

AC:

312581

AN:

1109746

Other (OTH)

AF:

0.371

AC:

22373

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

15136

30272

45408

60544

75680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.443

AC:

67157

AN:

151764

Hom.:

17939

Cov.:

AF XY:

0.442

AC XY:

32783

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.745

AC:

30850

AN:

41408

American (AMR)

AF:

0.345

AC:

5246

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1413

AN:

3468

East Asian (EAS)

AF:

0.698

AC:

3600

AN:

5154

South Asian (SAS)

AF:

0.453

AC:

2179

AN:

4814

European-Finnish (FIN)

AF:

0.292

AC:

3070

AN:

10496

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19609

AN:

67900

Other (OTH)

AF:

0.415

AC:

874

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1587

3174

4760

6347

7934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.331

Hom.:

5184

Bravo

AF:

0.462

Asia WGS

AF:

0.565

AC:

1967

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

-0.91

CADD

Benign

0.052

(source)

DANN

Benign

0.75

PhyloP100

-0.88

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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9-132278281-C-T

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