rs780658554
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PP2PP3PP5_StrongBS2
The NM_001130438.3(SPTAN1):c.2224C>T(p.Arg742Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,038 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. R742H) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.2224C>T | p.Arg742Cys | missense_variant | 17/57 | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.2224C>T | p.Arg742Cys | missense_variant | 17/57 | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251236Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135776
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461884Hom.: 0 Cov.: 37 AF XY: 0.0000151 AC XY: 11AN XY: 727246
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74324
ClinVar
Submissions by phenotype
Childhood epilepsy with centrotemporal spikes Pathogenic:1
Pathogenic, flagged submission | case-control | Bioinformatics Core, Luxembourg Center for Systems Biomedicine | Jan 01, 2017 | CAADphred>15 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | ClinVar contains an entry for this variant (Variation ID: 433112). This missense change has been observed in individual(s) with clinical features of SPTAN1-related conditions (PMID: 29358611). This variant is present in population databases (rs780658554, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 742 of the SPTAN1 protein (p.Arg742Cys). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at