rs430552
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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.1848C>T(p.Pro616=) 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 Benign (★★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIK1
NM_173354.5 synonymous
NM_173354.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.298
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=-0.8).
BP6
?
Variant 21-43417671-G-A is Benign according to our data. Variant chr21-43417671-G-A is described in ClinVar as [Benign]. Clinvar id is 586586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.298 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1848C>T | p.Pro616= | synonymous_variant | 13/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.1701C>T | p.Pro567= | synonymous_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1848C>T | p.Pro616= | synonymous_variant | 13/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 42124Hom.: 0 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.800 AC: 173778AN: 217226Hom.: 70096 AF XY: 0.796 AC XY: 94635AN XY: 118872
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 344962Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 171056
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 42124Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 19668
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 30, 2018 | - - |
Developmental and epileptic encephalopathy, 30 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 31, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 90. Only high quality variants are reported. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 31, 2015 | This alteration is classified as 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. - |
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