rs10892044

Positions:

• chr11-116896183-T-C

Variant summary

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

The NM_001366686.3(SIK3):​c.865+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,585,922 control chromosomes in the GnomAD database, including 17,944 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 0.16 (2021 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15923 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.865+70A>G		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.865+70A>G		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24105 AN: 152076 Hom.: 2012 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.145 AC: 208345 AN: 1433728 Hom.: 15923 AF XY: 0.146 AC XY: 103718 AN XY: 710286

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0505

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.159 AC: 24155 AN: 152194 Hom.: 2021 Cov.: 32 AF XY: 0.159 AC XY: 11836 AN XY: 74404

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.156

Alfa AF: 0.156 Hom.: 989

Bravo AF: 0.162

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10892044; hg19: chr11-116766899; COSMIC: COSV52620697;