rs11216162

Positions:

• chr11-116857561-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.3655+249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 536,616 control chromosomes in the GnomAD database, including 8,243 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 0.17 (2323 hom., cov: 32)
  • Exomes 𝑓: 0.17 (5920 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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=-0.87).
• 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.3655+249C>T		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.3655+249C>T		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25893 AN: 152058 Hom.: 2316 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.170 AC: 65435 AN: 384442 Hom.: 5920 Cov.: 6 AF XY: 0.173 AC XY: 34142 AN XY: 197806

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0847

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.170 AC: 25936 AN: 152174 Hom.: 2323 Cov.: 32 AF XY: 0.172 AC XY: 12823 AN XY: 74388

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.165

Alfa AF: 0.182 Hom.: 3548

Bravo AF: 0.167

Asia WGS AF: 0.191 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.21

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: rs11216162; hg19: chr11-116728277;