rs373872652
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_173354.5(SIK1):c.2049G>A(p.Pro683Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.000044 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
SIK1
NM_173354.5 synonymous
NM_173354.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.21
Genes affected
SIK1 (HGNC:11142): (salt inducible kinase 1) This gene encodes a serine/threonine protein kinase that contains a ubiquitin-associated (UBA) domain. The encoded protein is a member of the adenosine monophosphate-activated kinase (AMPK) subfamily of kinases that play a role in conserved signal transduction pathways. A mutation in this gene is associated with early infantile epileptic encephalopathy 30. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 21-43417045-C-T is Benign according to our data. Variant chr21-43417045-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43417045-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-3.21 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.2049G>A | p.Pro683Pro | synonymous_variant | 14/14 | ENST00000270162.8 | NP_775490.2 | |
SIK1 | XM_011529474.3 | c.1902G>A | p.Pro634Pro | synonymous_variant | 13/13 | XP_011527776.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.2049G>A | p.Pro683Pro | synonymous_variant | 14/14 | 1 | NM_173354.5 | ENSP00000270162.6 |
Frequencies
GnomAD3 genomes Cov.: 0
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GnomAD3 exomes AF: 0.000689 AC: 42AN: 60930Hom.: 1 AF XY: 0.000693 AC XY: 23AN XY: 33168
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000443 AC: 2AN: 45192Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 23320
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | SIK1: BP4, BP7 - |
Developmental and epileptic encephalopathy, 30 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at