Variant rs2296866 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SETX	NM_015046.7 linkuse as main transcript	c.6936-27T>G		intron_variant		ENST00000224140.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SETX	ENST00000224140.6 linkuse as main transcript	c.6936-27T>G	intron_variant	1	NM_015046.7	P1	Q7Z333-1
SETX	ENST00000436441.5 linkuse as main transcript	c.1662-27T>G	intron_variant	5
SETX	ENST00000464133.1 linkuse as main transcript	n.134-27T>G	intron_variant, non_coding_transcript_variant	2

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

GnomAD3 exomes

AF:

0.0378

AC:

8888

AN:

235298

Hom.:

393

AF XY:

0.0393

AC XY:

5007

AN XY:

127522

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 SAS exome

AF:

0.0562

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

Gnomad4 AFR exome

AF:

0.00421

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.0470

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.0573

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0224

Gnomad4 OTH exome

AF:

0.0396

GnomAD4 genome

AF:

0.0245

AC:

3729

AN:

152282

Hom.:

142

Cov.:

AF XY:

0.0249

AC XY:

1853

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.0670

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0240

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0256

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Amyotrophic lateral sclerosis type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.7

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over