rs518181

Positions:

• chr11-116902071-C-A

Variant summary

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

The NM_001366686.3(SIK3):​c.617-4754G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,086 control chromosomes in the GnomAD database, including 18,701 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 0.45 (18701 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.617-4754G>T		intron_variant		ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.617-4754G>T		intron_variant		5	NM_001366686.3	ENSP00000391295	A2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68421 AN: 151968 Hom.: 18705 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.450 AC: 68413 AN: 152086 Hom.: 18701 Cov.: 32 AF XY: 0.441 AC XY: 32789 AN XY: 74338

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.487

Alfa AF: 0.590 Hom.: 31826

Bravo AF: 0.435

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.82

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: rs518181; hg19: chr11-116772787;