rs147101451
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_173354.5(SIK1):c.1404G>A(p.Thr468=) 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)
Consequence
SIK1
NM_173354.5 synonymous
NM_173354.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.16
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 21-43419079-C-T is Benign according to our data. Variant chr21-43419079-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43419079-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.16 with no splicing effect.
BS2
?
High AC in GnomAdExome at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1404G>A | p.Thr468= | synonymous_variant | 11/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.1257G>A | p.Thr419= | synonymous_variant | 10/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1404G>A | p.Thr468= | synonymous_variant | 11/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD3 exomes AF: 0.0000976 AC: 14AN: 143432Hom.: 0 AF XY: 0.0000784 AC XY: 6AN XY: 76502
GnomAD3 exomes
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14
AN:
143432
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AC XY:
6
AN XY:
76502
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GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 0
GnomAD4 genome
?
Cov.:
0
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
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 | May 30, 2017 | 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. - |
Developmental and epileptic encephalopathy, 30 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Calibrated prediction
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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