rs1555891321
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_173354.5(SIK1):c.709C>G(p.Leu237Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. L237P) has been classified as Uncertain significance.
Frequency
Consequence
NM_173354.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.709C>G | p.Leu237Val | missense_variant | 7/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.709C>G | p.Leu237Val | missense_variant | 7/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.709C>G | p.Leu237Val | missense_variant | 7/14 | 1 | NM_173354.5 | P1 | |
SIK1 | ENST00000644689.1 | n.511C>G | non_coding_transcript_exon_variant | 4/5 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD4 exome Cov.: 0
GnomAD4 genome ? Cov.: 0
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2020 | This variant has not been reported in the literature in individuals with SIK1-related disease. 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 missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 237 of the SIK1 protein (p.Leu237Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at