chr9-132264368-G-A
Position:
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
NM_015046.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.01
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 |
---|---|---|---|---|---|---|---|
SETX | NM_015046.7 | c.7905C>T | p.Ala2635= | synonymous_variant | 26/26 | ENST00000224140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.7905C>T | p.Ala2635= | synonymous_variant | 26/26 | 1 | NM_015046.7 | P1 | |
SETX | ENST00000436441.5 | c.2718C>T | p.Ala906= | synonymous_variant | 17/17 | 5 | |||
SETX | ENST00000477049.1 | n.1055C>T | non_coding_transcript_exon_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00582 AC: 885AN: 152118Hom.: 6 Cov.: 31
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:
GnomAD3 exomes AF: 0.00155 AC: 391AN: 251484Hom.: 5 AF XY: 0.00116 AC XY: 158AN XY: 135916
GnomAD3 exomes
AF:
AC:
391
AN:
251484
Hom.:
AF XY:
AC XY:
158
AN XY:
135916
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000552 AC: 807AN: 1461894Hom.: 10 Cov.: 30 AF XY: 0.000468 AC XY: 340AN XY: 727248
GnomAD4 exome
AF:
AC:
807
AN:
1461894
Hom.:
Cov.:
30
AF XY:
AC XY:
340
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00582 AC: 886AN: 152236Hom.: 6 Cov.: 31 AF XY: 0.00540 AC XY: 402AN XY: 74426
GnomAD4 genome
AF:
AC:
886
AN:
152236
Hom.:
Cov.:
31
AF XY:
AC XY:
402
AN XY:
74426
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
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
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 01, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 13, 2020 | - - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 03, 2024 | - - |
Amyotrophic lateral sclerosis type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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