rs142171557
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_173354.5(SIK1):c.1553C>G(p.Ala518Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 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. A518P) has been classified as Likely benign.
Frequency
Consequence
NM_173354.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1553C>G | p.Ala518Gly | missense_variant | 12/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.1406C>G | p.Ala469Gly | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1553C>G | p.Ala518Gly | missense_variant | 12/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243384Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132654
GnomAD4 exome Cov.: 0
GnomAD4 genome ? Cov.: 0
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2022 | The c.1553C>G (p.A518G) alteration is located in exon 12 (coding exon 11) of the SIK1 gene. This alteration results from a C to G substitution at nucleotide position 1553, causing the alanine (A) at amino acid position 518 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Developmental and epileptic encephalopathy, 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 518 of the SIK1 protein (p.Ala518Gly). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 1021126). 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. 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