chr9-132264368-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015046.7(SETX):​c.7905C>T​(p.Ala2635=) 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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr9-132264368-G-A is described in Lovd as [Benign].
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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SETXNM_015046.7 linkuse as main transcriptc.7905C>T p.Ala2635= synonymous_variant 26/26 ENST00000224140.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SETXENST00000224140.6 linkuse as main transcriptc.7905C>T p.Ala2635= synonymous_variant 26/261 NM_015046.7 P1Q7Z333-1
SETXENST00000436441.5 linkuse as main transcriptc.2718C>T p.Ala906= synonymous_variant 17/175
SETXENST00000477049.1 linkuse as main transcriptn.1055C>T non_coding_transcript_exon_variant 5/53

Frequencies

GnomAD3 genomes
AF:
0.00582
AC:
885
AN:
152118
Hom.:
6
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0204
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00155
AC:
391
AN:
251484
Hom.:
5
AF XY:
0.00116
AC XY:
158
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.0225
Gnomad AMR exome
AF:
0.000549
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000552
AC:
807
AN:
1461894
Hom.:
10
Cov.:
30
AF XY:
0.000468
AC XY:
340
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0210
Gnomad4 AMR exome
AF:
0.000760
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.000944
GnomAD4 genome
AF:
0.00582
AC:
886
AN:
152236
Hom.:
6
Cov.:
31
AF XY:
0.00540
AC XY:
402
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0204
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00319
Hom.:
1
Bravo
AF:
0.00649
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJun 01, 2021- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 30, 2021- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 13, 2020- -
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 03, 2024- -
Amyotrophic lateral sclerosis type 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
2.8
DANN
Benign
0.53

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.

Other links and lift over

dbSNP: rs112201716; hg19: chr9-135139755; API