Variant chr11-116857914-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001366686.3(SIK3):c.3551C>G(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 (★★).

Frequency

Genomes: 𝑓 0.17 ( 2320 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24501 hom. )

Consequence

SIK3
NM_001366686.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.16

Variant links:

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]

SIK3 links:

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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 linkuse as main transcript	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 linkuse as main transcript	c.3551C>G	p.Pro1184Arg	missense_variant	21/25	5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25891

AN:

151984

Hom.:

2312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0938

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.188

AC:

47169

AN:

251452

Hom.:

4709

AF XY:

0.190

AC XY:

25778

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.0943

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.180

AC:

262609

AN:

1461858

Hom.:

24501

Cov.:

AF XY:

0.182

AC XY:

132296

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.0904

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.171

AC:

25936

AN:

152102

Hom.:

2320

Cov.:

AF XY:

0.172

AC XY:

12824

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0940

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.161

Hom.:

1340

Bravo

AF:

0.167

TwinsUK

AF:

0.186

AC:

688

ALSPAC

AF:

0.177

AC:

684

ESP6500AA

AF:

0.137

AC:

603

ESP6500EA

AF:

0.173

AC:

1488

ExAC

AF:

0.187

AC:

22701

Asia WGS

AF:

0.191

AC:

661

AN:

3478

EpiCase

AF:

0.180

EpiControl

AF:

0.176

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SIK3-related disorder

Benign:1

Benign, no assertion criteria provided

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Spondyloepimetaphyseal dysplasia, Krakow type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.0021

P;P;P;P;P;P

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.038

D;D

Vest4

0.53

ClinPred

0.034

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over