rs1160694512
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate
The NM_001130438.3(SPTAN1):c.7375C>T(p.Arg2459Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,906 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2459H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130438.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.7375C>T | p.Arg2459Cys | missense_variant | 57/57 | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.7375C>T | p.Arg2459Cys | missense_variant | 57/57 | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251244Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135850
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461772Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727196
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2459 of the SPTAN1 protein (p.Arg2459Cys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPTAN1 protein function. ClinVar contains an entry for this variant (Variation ID: 530529). This variant has not been reported in the literature in individuals affected with SPTAN1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at