Variant 9-132261977-T-C 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.*2262A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 154,414 control chromosomes in the GnomAD database, including 818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 763 hom., cov: 33)

Exomes 𝑓: 0.20 ( 55 hom. )

Consequence

SETX
NM_015046.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.38

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=-0.89).

BP6

Variant 9-132261977-T-C is Benign according to our data. Variant chr9-132261977-T-C is described in ClinVar as [Benign]. Clinvar id is 365305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETX	NM_015046.7 link	c.*2262A>G		3_prime_UTR_variant	Exon 26 of 26	ENST00000224140.6	NP_055861.3	Q7Z333-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SETX	ENST00000224140 link	c.*2262A>G	3_prime_UTR_variant	Exon 26 of 26	1	NM_015046.7	ENSP00000224140.5	Q7Z333-1
SETX	ENST00000436441 link	c.*2262A>G	3_prime_UTR_variant	Exon 17 of 17	5		ENSP00000409143.1	X6RI79
SETX	ENST00000477049.1 link	n.3446A>G	non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0948

AC:

14417

AN:

152128

Hom.:

761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0820

Gnomad OTH

AF:

0.0965

GnomAD4 exome

AF:

0.196

AC:

425

AN:

2168

Hom.:

Cov.:

AF XY:

0.181

AC XY:

196

AN XY:

1084

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0769

Gnomad4 OTH exome

AF:

0.0904

GnomAD4 genome

AF:

0.0948

AC:

14430

AN:

152246

Hom.:

763

Cov.:

AF XY:

0.0951

AC XY:

7080

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0703

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0522

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.0820

Gnomad4 OTH

AF:

0.0950

Alfa

AF:

0.0888

Hom.:

529

Bravo

AF:

0.0943

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 4

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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:2

Feb 08, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

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

-0.89

CADD

Benign

0.15

DANN

Benign

0.44

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