rs11216185

Positions:

• chr11-116912258-T-G

Variant summary

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

The NM_001366686.3(SIK3):​c.617-14941A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 152,228 control chromosomes in the GnomAD database, including 503 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 0.074 (503 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.617-14941A>C		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.617-14941A>C		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11297 AN: 152110 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0590

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

GnomAD4 genome AF: 0.0742 AC: 11289 AN: 152228 Hom.: 503 Cov.: 32 AF XY: 0.0741 AC XY: 5512 AN XY: 74416

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0402

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0789

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0628 Hom.: 689

Bravo AF: 0.0746

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.74

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: rs11216185; hg19: chr11-116782974;