rs12292858

chr11-116943263-A-Cchr11-116943263-A-G

Variant summary

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

The NM_001366686.3(SIK3):c.454+10781T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,086 control chromosomes in the GnomAD database, including 2,255 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 0.15 (2255 hom., cov: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.454+10781T>G		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.454+10781T>G		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22172 AN: 151968 Hom.: 2257 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.146 AC: 22171 AN: 152086 Hom.: 2255 Cov.: 31 AF XY: 0.146 AC XY: 10871 AN XY: 74354

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0739

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0893

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0585 Hom.: 74

Bravo AF: 0.152

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.5
Dann	Benign	0.78

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: rs12292858; hg19: chr11-116813979;