chr11-116857914-G-C
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_001366686.3(SIK3):āc.3551C>Gā(p.Pro1184Arg) variant causes a missense change. The variant allele was found at a frequency of 0.179 in 1,613,960 control chromosomes in the GnomAD database, including 26,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.17 ( 2320 hom., cov: 32)
Exomes š: 0.18 ( 24501 hom. )
Consequence
SIK3
NM_001366686.3 missense
NM_001366686.3 missense
Scores
1
7
8
Clinical Significance
Conservation
PhyloP100: 5.16
Genes affected
SIK3 (HGNC:29165): (SIK family kinase 3) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in positive regulation of TORC1 signaling; positive regulation of TORC2 signaling; and protein phosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SIK3. . Trascript score misZ 3.9277 (greater than threshold 3.09). GenCC has associacion of gene with spondyloepimetaphyseal dysplasia, Krakow type.
BP4
Computational evidence support a benign effect (MetaRNN=0.0016655326).
BP6
Variant 11-116857914-G-C is Benign according to our data. Variant chr11-116857914-G-C is described in ClinVar as [Benign]. Clinvar id is 1332964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK3 | NM_001366686.3 | c.3551C>G | p.Pro1184Arg | missense_variant | 21/25 | ENST00000445177.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK3 | ENST00000445177.6 | c.3551C>G | p.Pro1184Arg | missense_variant | 21/25 | 5 | NM_001366686.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.170 AC: 25891AN: 151984Hom.: 2312 Cov.: 32
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GnomAD3 exomes AF: 0.188 AC: 47169AN: 251452Hom.: 4709 AF XY: 0.190 AC XY: 25778AN XY: 135894
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GnomAD4 exome AF: 0.180 AC: 262609AN: 1461858Hom.: 24501 Cov.: 33 AF XY: 0.182 AC XY: 132296AN XY: 727230
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GnomAD4 genome AF: 0.171 AC: 25936AN: 152102Hom.: 2320 Cov.: 32 AF XY: 0.172 AC XY: 12824AN XY: 74366
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SIK3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Spondyloepimetaphyseal dysplasia, Krakow type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Vest4
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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