rs756290749
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001130438.3(SPTAN1):āc.649C>Gā(p.Gln217Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000124 in 1,611,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001130438.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.649C>G | p.Gln217Glu | missense_variant, splice_region_variant | 5/57 | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.649C>G | p.Gln217Glu | missense_variant, splice_region_variant | 5/57 | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1458900Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 725910
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 24, 2024 | Variant summary: SPTAN1 c.649C>G (p.Gln217Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 248416 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.649C>G in individuals affected with Epileptic Encephalopathy, Early Infantile, 5 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 530542). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2020 | The p.Q217E variant (also known as c.649C>G), located in coding exon 4 of the SPTAN1 gene, results from a C to G substitution at nucleotide position 649. The glutamine at codon 217 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 05, 2017 | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SPTAN1-related disease. This sequence change replaces glutamine with glutamic acid at codon 217 of the SPTAN1 protein (p.Gln217Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at