chr9-132342660-A-G

Variant names:

• chr9-132342660-A-G
• rs11790312
• NM_015046.7:c.498+30T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.31
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• distal hereditary motor neuropathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 260508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015046.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETX	NM_015046.7	MANE Select	c.498+30T>C		intron	N/A	NP_055861.3
	SETX	NM_001351528.2		c.498+30T>C		intron	N/A	NP_001338457.1	Q7Z333-4
	SETX	NM_001351527.2		c.498+30T>C		intron	N/A	NP_001338456.1	Q7Z333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETX	ENST00000224140.6	TSL:1 MANE Select	c.498+30T>C		intron	N/A	ENSP00000224140.5	Q7Z333-1
	SETX	ENST00000923216.1		c.498+30T>C		intron	N/A	ENSP00000593275.1
	SETX	ENST00000923217.1		c.498+30T>C		intron	N/A	ENSP00000593276.1

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8973 AN: 152002 Hom.: 383 Cov.: 32

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

GnomAD2 exomes AF: 0.0712 AC: 17872 AN: 251000 AF XY: 0.0690

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 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.: 18 AF XY: 0.0539 AC XY: 34255 AN XY: 635022

African (AFR) AF: 0.0605 AC: 1777 AN: 29396

American (AMR) AF: 0.0733 AC: 3261 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.0382 AC: 949 AN: 24846

East Asian (EAS) AF: 0.247 AC: 9525 AN: 38626

South Asian (SAS) AF: 0.0709 AC: 5815 AN: 82036

European-Finnish (FIN) AF: 0.0557 AC: 2961 AN: 53172

Middle Eastern (MID) AF: 0.0480 AC: 257 AN: 5358

European-Non Finnish (NFE) AF: 0.0433 AC: 39978 AN: 923076

Other (OTH) AF: 0.0544 AC: 2918 AN: 53608

GnomAD4 genome AF: 0.0590 AC: 8977 AN: 152120 Hom.: 382 Cov.: 32 AF XY: 0.0599 AC XY: 4459 AN XY: 74386

African (AFR) AF: 0.0628 AC: 2605 AN: 41486

American (AMR) AF: 0.0561 AC: 856 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1319 AN: 5164

South Asian (SAS) AF: 0.0735 AC: 354 AN: 4816

European-Finnish (FIN) AF: 0.0501 AC: 531 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3019 AN: 68010

Other (OTH) AF: 0.0508 AC: 107 AN: 2108

Alfa AF: 0.0501 Hom.: 40

Bravo AF: 0.0613

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Amyotrophic lateral sclerosis type 4 (1)
-	-	1	not specified (1)
-	-	1	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.40
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11790312; hg19: chr9-135218047; COSMIC: COSV56381066;