rs372193033
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BP6
The NM_015046.7(SETX):c.968G>A(p.Ser323Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000222 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S323G) has been classified as Uncertain significance.
Frequency
Consequence
NM_015046.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETX | NM_015046.7 | c.968G>A | p.Ser323Asn | missense_variant | 8/26 | ENST00000224140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.968G>A | p.Ser323Asn | missense_variant | 8/26 | 1 | NM_015046.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000219 AC: 55AN: 251440Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135884
GnomAD4 exome AF: 0.000227 AC: 332AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.000209 AC XY: 152AN XY: 727216
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74308
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | SETX: PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2023 | Previously reported in an individual with apparently sporadic ALS, who also harbored a variant in a different gene associated with ALS (PMID: 25382069); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25869998, 29605155, 25382069) - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 02, 2022 | Unlikely to be causative of SETX-related juvenile amyotrophic lateral sclerosis (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 24, 2021 | - - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at