rs533556

chr11-116870856-A-C

Variant summary

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

The NM_001366686.3(SIK3):c.1738-455T>G 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 152,018 control chromosomes in the GnomAD database, including 18,609 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 (18609 hom., cov: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.1738-455T>G		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.1738-455T>G		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68395 AN: 151900 Hom.: 18614 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.450 AC: 68383 AN: 152018 Hom.: 18609 Cov.: 31 AF XY: 0.442 AC XY: 32853 AN XY: 74280

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.484

Alfa AF: 0.561 Hom.: 12637

Bravo AF: 0.435

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.1
Dann	Benign	0.76

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: rs533556; hg19: chr11-116741572;