rs376891838
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_173354.5(SIK1):c.862G>A(p.Ala288Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/23 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. A288S) has been classified as Uncertain significance.
Frequency
Consequence
NM_173354.5 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 |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.862G>A | p.Ala288Thr | missense_variant | 8/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.862G>A | p.Ala288Thr | missense_variant | 8/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.862G>A | p.Ala288Thr | missense_variant | 8/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247306Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134440
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 504Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 278
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 16, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 288 of the SIK1 protein (p.Ala288Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SIK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 950478). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SIK1 protein function with a negative predictive value of 95%. 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