rs11216257

Variant names:

• chr11-117061845-C-T
• rs11216257
• NM_001366686.3:c.273+36298G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366686.3(SIK3):​c.273+36298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 151,986 control chromosomes in the GnomAD database, including 44,037 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 0.75 (44037 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 12 publications found

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]

SIK3 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• spondyloepimetaphyseal dysplasia, Krakow type

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.273+36298G>A		intron_variant	Intron 1 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.273+36298G>A		intron_variant	Intron 1 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114679 AN: 151868 Hom.: 44009 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.755 AC: 114745 AN: 151986 Hom.: 44037 Cov.: 32 AF XY: 0.748 AC XY: 55552 AN XY: 74284

African (AFR) AF: 0.699 AC: 28959 AN: 41452

American (AMR) AF: 0.745 AC: 11359 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2555 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2016 AN: 5154

South Asian (SAS) AF: 0.592 AC: 2850 AN: 4818

European-Finnish (FIN) AF: 0.748 AC: 7873 AN: 10528

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56507 AN: 67990

Other (OTH) AF: 0.763 AC: 1614 AN: 2114

Alfa AF: 0.803 Hom.: 82792

Bravo AF: 0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.68
DANN	Benign	0.65
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11216257; hg19: chr11-116932561;