chr9-132300812-CAAG-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_015046.7(SETX):​c.5375-12_5375-10delCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,610,992 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 15 hom., cov: 32)
Exomes 𝑓: 0.00067 ( 6 hom. )

Consequence

SETX
NM_015046.7 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 2.10

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • amyotrophic lateral sclerosis type 4
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6
Variant 9-132300812-CAAG-C is Benign according to our data. Variant chr9-132300812-CAAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 468517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00543 (826/152082) while in subpopulation AFR AF = 0.0185 (766/41512). AF 95% confidence interval is 0.0174. There are 15 homozygotes in GnomAd4. There are 413 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 15 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETXNM_015046.7 linkc.5375-12_5375-10delCTT intron_variant Intron 11 of 25 ENST00000224140.6 NP_055861.3 Q7Z333-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETXENST00000224140.6 linkc.5375-12_5375-10delCTT intron_variant Intron 11 of 25 1 NM_015046.7 ENSP00000224140.5 Q7Z333-1
SETXENST00000436441.5 linkc.101-12_101-10delCTT intron_variant Intron 1 of 16 5 ENSP00000409143.1 X6RI79

Frequencies

GnomAD3 genomes
AF:
0.00541
AC:
822
AN:
151964
Hom.:
15
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0184
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00526
GnomAD2 exomes
AF:
0.00153
AC:
380
AN:
248510
AF XY:
0.00124
show subpopulations
Gnomad AFR exome
AF:
0.0175
Gnomad AMR exome
AF:
0.00134
Gnomad ASJ exome
AF:
0.00140
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000204
Gnomad OTH exome
AF:
0.00115
GnomAD4 exome
AF:
0.000668
AC:
974
AN:
1458910
Hom.:
6
AF XY:
0.000606
AC XY:
440
AN XY:
725878
show subpopulations
African (AFR)
AF:
0.0178
AC:
594
AN:
33406
American (AMR)
AF:
0.00161
AC:
72
AN:
44584
Ashkenazi Jewish (ASJ)
AF:
0.00130
AC:
34
AN:
26090
East Asian (EAS)
AF:
0.0000253
AC:
1
AN:
39558
South Asian (SAS)
AF:
0.000268
AC:
23
AN:
85964
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52402
Middle Eastern (MID)
AF:
0.00177
AC:
10
AN:
5660
European-Non Finnish (NFE)
AF:
0.000127
AC:
141
AN:
1110978
Other (OTH)
AF:
0.00164
AC:
99
AN:
60268
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.456
Heterozygous variant carriers
0
41
82
124
165
206
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
22
44
66
88
110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00543
AC:
826
AN:
152082
Hom.:
15
Cov.:
32
AF XY:
0.00556
AC XY:
413
AN XY:
74330
show subpopulations
African (AFR)
AF:
0.0185
AC:
766
AN:
41512
American (AMR)
AF:
0.00236
AC:
36
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.000577
AC:
2
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.000416
AC:
2
AN:
4808
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10552
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.000118
AC:
8
AN:
67994
Other (OTH)
AF:
0.00520
AC:
11
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
41
82
123
164
205
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00269
Hom.:
0
Bravo
AF:
0.00577
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Mar 13, 2020
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 25, 2018
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 29, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hereditary spastic paraplegia Benign:1
Aug 01, 2019
Genome Diagnostics Laboratory, The Hospital for Sick Children
Significance:Likely 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

- -

SETX-related disorder Benign:1
Feb 20, 2020
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:1
Feb 08, 2023
Genome-Nilou Lab
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.1
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs201317659; hg19: chr9-135176199; API