9-132275229-T-C

Variant names:

Variant summary

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

The NM_015046.7(SETX):c.7100+27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,607,116 control chromosomes in the GnomAD database, including 19,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2655 hom., cov: 32)

Exomes 𝑓: 0.13 ( 17234 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.583

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=-0.88).

BP6

Variant 9-132275229-T-C is Benign according to our data. Variant chr9-132275229-T-C is described in ClinVar as [Benign]. Clinvar id is 260516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132275229-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.7100+27A>G		intron_variant	Intron 23 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.7100+27A>G	intron_variant	Intron 23 of 25	1	NM_015046.7	ENSP00000224140.5	Q7Z333-1
SETX	ENST00000436441.5 link	c.1826+27A>G	intron_variant	Intron 13 of 16	5		ENSP00000409143.1	X6RI79
SETX	ENST00000464133.1 link	n.325A>G	non_coding_transcript_exon_variant	Exon 3 of 3	2
SETX	ENST00000477049.1 link	n.127+27A>G	intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25615

AN:

151998

Hom.:

2654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.171

AC:

42922

AN:

250898

Hom.:

4781

AF XY:

0.173

AC XY:

23448

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.431

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.134

AC:

195373

AN:

1455000

Hom.:

17234

Cov.:

AF XY:

0.138

AC XY:

100111

AN XY:

724314

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.457

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.169

AC:

25643

AN:

152116

Hom.:

2655

Cov.:

AF XY:

0.173

AC XY:

12850

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.427

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.133

Hom.:

448

Bravo

AF:

0.174

Asia WGS

AF:

0.348

AC:

1208

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.88

CADD

Benign

5.1

DANN

Benign

0.59

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