Variant 9-132283232-A-T 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.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

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=-0.71).

BP6

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

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/exons	MANE	Protein	UniProt
SETX	NM_015046.7 linkuse as main transcript	c.6546+32T>A		intron_variant		ENST00000224140.6	NP_055861.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETX	ENST00000224140.6 linkuse as main transcript	c.6546+32T>A	intron_variant		1	NM_015046.7	ENSP00000224140	P1	Q7Z333-1
SETX	ENST00000436441.5 linkuse as main transcript	c.1272+32T>A	intron_variant		5		ENSP00000409143
SETX	ENST00000474172.1 linkuse as main transcript	n.257T>A	non_coding_transcript_exon_variant	2/2	3

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

GnomAD3 exomes

AF:

0.0830

AC:

20863

AN:

251328

Hom.:

1981

AF XY:

0.0794

AC XY:

10793

AN XY:

135848

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 SAS exome

AF:

0.107

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

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.0975

Gnomad4 ASJ exome

AF:

0.0488

Gnomad4 EAS exome

AF:

0.406

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0450

Gnomad4 NFE exome

AF:

0.0256

Gnomad4 OTH exome

AF:

0.0697

GnomAD4 genome

AF:

0.0755

AC:

11494

AN:

152182

Hom.:

833

Cov.:

AF XY:

0.0791

AC XY:

5887

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0704

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0469

Gnomad4 NFE

AF:

0.0276

Gnomad4 OTH

AF:

0.0700

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

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

-0.71

CADD

Benign

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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