9-132329316-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_015046.7(SETX):​c.2282C>G​(p.Ser761Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SETX
NM_015046.7 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49
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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETXNM_015046.7 linkc.2282C>G p.Ser761Trp missense_variant Exon 10 of 26 ENST00000224140.6 NP_055861.3 Q7Z333-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETXENST00000224140.6 linkc.2282C>G p.Ser761Trp missense_variant Exon 10 of 26 1 NM_015046.7 ENSP00000224140.5 Q7Z333-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250894
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461512
Hom.:
0
Cov.:
36
AF XY:
0.00000550
AC XY:
4
AN XY:
727036
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SETX-related disorder Uncertain:1
May 02, 2023
PreventionGenetics, part of Exact Sciences
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The SETX c.2282C>G variant is predicted to result in the amino acid substitution p.Ser761Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-135204703-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Uncertain
0.081
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T
Eigen
Benign
0.18
Eigen_PC
Benign
0.082
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.065
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Benign
2.0
M
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.050
N
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.51
MutPred
0.20
Loss of phosphorylation at S761 (P = 0.0143);
MVP
0.85
MPC
0.49
ClinPred
0.78
D
GERP RS
4.7
Varity_R
0.11
gMVP
0.36

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: rs200153024; hg19: chr9-135204703; API