rs482371

Positions:

• chr11-116881447-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.866-4405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,162 control chromosomes in the GnomAD database, including 18,900 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 (18900 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.866-4405A>G		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.866-4405A>G		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68950 AN: 152042 Hom.: 18905 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.453 AC: 68938 AN: 152162 Hom.: 18900 Cov.: 32 AF XY: 0.445 AC XY: 33116 AN XY: 74396

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.490

Alfa AF: 0.564 Hom.: 16882

Bravo AF: 0.438

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs482371; hg19: chr11-116752163;