rs112201716
Variant names:
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015046.7(SETX):c.7905C>T(p.Ala2635Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,614,130 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0058 ( 6 hom., cov: 31)
Exomes 𝑓: 0.00055 ( 10 hom. )
Consequence
SETX
NM_015046.7 synonymous
NM_015046.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.01
Publications
0 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 4Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
- distal hereditary motor neuropathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2Inheritance: 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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 9-132264368-G-A is Benign according to our data. Variant chr9-132264368-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.01 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00582 (886/152236) while in subpopulation AFR AF = 0.0204 (846/41530). AF 95% confidence interval is 0.0192. There are 6 homozygotes in GnomAd4. There are 402 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 6 AR,AD gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.7905C>T | p.Ala2635Ala | synonymous_variant | Exon 26 of 26 | 1 | NM_015046.7 | ENSP00000224140.5 | ||
SETX | ENST00000436441.5 | c.2718C>T | p.Ala906Ala | synonymous_variant | Exon 17 of 17 | 5 | ENSP00000409143.1 | |||
SETX | ENST00000477049.1 | n.1055C>T | non_coding_transcript_exon_variant | Exon 5 of 5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00582 AC: 885AN: 152118Hom.: 6 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
885
AN:
152118
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00155 AC: 391AN: 251484 AF XY: 0.00116 show subpopulations
GnomAD2 exomes
AF:
AC:
391
AN:
251484
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000552 AC: 807AN: 1461894Hom.: 10 Cov.: 30 AF XY: 0.000468 AC XY: 340AN XY: 727248 show subpopulations
GnomAD4 exome
AF:
AC:
807
AN:
1461894
Hom.:
Cov.:
30
AF XY:
AC XY:
340
AN XY:
727248
show subpopulations
African (AFR)
AF:
AC:
702
AN:
33480
American (AMR)
AF:
AC:
34
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
3
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
2
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1112012
Other (OTH)
AF:
AC:
57
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
58
115
173
230
288
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00582 AC: 886AN: 152236Hom.: 6 Cov.: 31 AF XY: 0.00540 AC XY: 402AN XY: 74426 show subpopulations
GnomAD4 genome
AF:
AC:
886
AN:
152236
Hom.:
Cov.:
31
AF XY:
AC XY:
402
AN XY:
74426
show subpopulations
African (AFR)
AF:
AC:
846
AN:
41530
American (AMR)
AF:
AC:
25
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4812
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
4
AN:
68020
Other (OTH)
AF:
AC:
11
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
38
77
115
154
192
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
7
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Jun 01, 2021
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
Clinical Genetics, Academic Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
not provided Benign:2
Mar 30, 2021
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
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
- -
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Jan 20, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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:Likely 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:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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