rs754872537
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6_Moderate
The NM_173354.5(SIK1):āc.1043A>Gā(p.Tyr348Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0 ( 0 hom., cov: 0)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIK1
NM_173354.5 missense
NM_173354.5 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 3.54
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 Likely_benign. Variant got -3 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2842434).
BP6
?
Variant 21-43419935-T-C is Benign according to our data. Variant chr21-43419935-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 542702.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1043A>G | p.Tyr348Cys | missense_variant | 9/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.972+299A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1043A>G | p.Tyr348Cys | missense_variant | 9/14 | 1 | NM_173354.5 | P1 | |
SIK1 | ENST00000644871.1 | upstream_gene_variant |
Frequencies
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GnomAD3 exomes AF: 0.0000215 AC: 5AN: 232686Hom.: 0 AF XY: 0.0000238 AC XY: 3AN XY: 126300
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 37406Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 20234
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 2770Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 1226
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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 | Oct 03, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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