rs142866662
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_173354.5(SIK1):c.1463-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIK1
NM_173354.5 splice_region, splice_polypyrimidine_tract, intron
NM_173354.5 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00003004
2
Clinical Significance
Conservation
PhyloP100: 0.471
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 21-43418548-G-A is Benign according to our data. Variant chr21-43418548-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 476084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1463-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000270162.8 | |||
SIK1 | XM_011529474.3 | c.1316-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1463-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00340 AC: 815AN: 239724Hom.: 5 AF XY: 0.00328 AC XY: 430AN XY: 130942
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1788Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 968
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
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3478
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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
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 14, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SIK1: BP4, BS2 - |
Developmental and epileptic encephalopathy, 30 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at