Variant 11-116863829-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBA1

The NM_001366686.3(SIK3):c.1953-11C>T variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.287 in 1,590,200 control chromosomes in the GnomAD database, including 73,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4819 hom., cov: 32)

Exomes 𝑓: 0.29 ( 68285 hom. )

Consequence

SIK3
NM_001366686.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.9384

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.95

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.18).

BP6

Variant 11-116863829-G-A is Benign according to our data. Variant chr11-116863829-G-A is described in ClinVar as [Benign]. Clinvar id is 1332966.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 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.1953-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6 linkuse as main transcript	c.1953-11C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33243

AN:

152038

Hom.:

4821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0257

Gnomad SAS

AF:

0.0836

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.232

AC:

53913

AN:

232600

Hom.:

7837

AF XY:

0.236

AC XY:

29520

AN XY:

125248

show subpopulations

Gnomad AFR exome

AF:

0.0572

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.0224

Gnomad SAS exome

AF:

0.0914

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.295

AC:

423545

AN:

1438044

Hom.:

68285

Cov.:

AF XY:

0.290

AC XY:

206468

AN XY:

712986

show subpopulations

Gnomad4 AFR exome

AF:

0.0520

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.0190

Gnomad4 SAS exome

AF:

0.0931

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.218

AC:

33238

AN:

152156

Hom.:

4819

Cov.:

AF XY:

0.210

AC XY:

15593

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0623

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.0252

Gnomad4 SAS

AF:

0.0854

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.293

Hom.:

8336

Bravo

AF:

0.211

Asia WGS

AF:

0.0550

AC:

194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.94

dbscSNV1_RF

Benign

0.71

SpliceAI score (max)

0.0

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