rs11216230

Positions:

• chr11-117014073-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366686.3(SIK3):​c.274-57009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 136,296 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (173 hom., cov: 27)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.274-57009C>T		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.274-57009C>T		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 4629 AN: 136206 Hom.: 174 Cov.: 27

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.00647

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0339 AC: 4626 AN: 136296 Hom.: 173 Cov.: 27 AF XY: 0.0386 AC XY: 2521 AN XY: 65358

Gnomad4 AFR AF: 0.00803

Gnomad4 AMR AF: 0.0960

Gnomad4 ASJ AF: 0.00647

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0275 Hom.: 18

Bravo AF: 0.0355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.1
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs11216230; hg19: chr11-116884789;