dbSNP rs11790312: SETX:c.498+30T>C (chr9-132342660-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015046.7(SETX):c.498+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,406,720 control chromosomes in the GnomAD database, including 3,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 382 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2779 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.31

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=-0.9).

BP6

Variant 9-132342660-A-G is Benign according to our data. Variant chr9-132342660-A-G is described in ClinVar as [Benign]. Clinvar id is 260508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132342660-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.498+30T>C		intron_variant	Intron 5 of 25	ENST00000224140.6	NP_055861.3	Q7Z333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETX	ENST00000224140.6 link	c.498+30T>C		intron_variant	Intron 5 of 25	1	NM_015046.7	ENSP00000224140.5		Q7Z333-1

Frequencies

GnomAD3 genomes

AF:

0.0590

AC:

8973

AN:

152002

Hom.:

383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.0737

Gnomad FIN

AF:

0.0501

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0444

Gnomad OTH

AF:

0.0523

GnomAD3 exomes

AF:

0.0712

AC:

17872

AN:

251000

Hom.:

1078

AF XY:

0.0690

AC XY:

9370

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0637

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.0357

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.0719

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0543

GnomAD4 exome

AF:

0.0538

AC:

67441

AN:

1254600

Hom.:

2779

Cov.:

AF XY:

0.0539

AC XY:

34255

AN XY:

635022

show subpopulations

Gnomad4 AFR exome

AF:

0.0605

Gnomad4 AMR exome

AF:

0.0733

Gnomad4 ASJ exome

AF:

0.0382

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.0709

Gnomad4 FIN exome

AF:

0.0557

Gnomad4 NFE exome

AF:

0.0433

Gnomad4 OTH exome

AF:

0.0544

GnomAD4 genome

AF:

0.0590

AC:

8977

AN:

152120

Hom.:

382

Cov.:

AF XY:

0.0599

AC XY:

4459

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0628

Gnomad4 AMR

AF:

0.0561

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.0735

Gnomad4 FIN

AF:

0.0501

Gnomad4 NFE

AF:

0.0444

Gnomad4 OTH

AF:

0.0508

Alfa

AF:

0.0500

Hom.:

Bravo

AF:

0.0613

Asia WGS

AF:

0.137

AC:

475

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

-0.90

CADD

Benign

0.026

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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