rs375664122
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_173354.5(SIK1):c.1463-5C>G 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: 0.00007125
2
Clinical Significance
Conservation
PhyloP100: -0.256
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 21-43418546-G-C is Benign according to our data. Variant chr21-43418546-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 542728.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1463-5C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000270162.8 | |||
SIK1 | XM_011529474.3 | c.1316-5C>G | 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.1463-5C>G | 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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0
GnomAD3 exomes AF: 0.000150 AC: 36AN: 239872Hom.: 0 AF XY: 0.000168 AC XY: 22AN XY: 130974
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1938Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 1054
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 30 Benign:1
Likely 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
Name
Calibrated prediction
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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