rs11216230

Variant names:

• chr11-117014073-G-A
• rs11216230
• NM_001366686.3:c.274-57009C>T

Variant summary

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

The NM_001366686.3(SIK3):​c.274-57009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 136,296 control chromosomes in the GnomAD database, including 173 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 0.034 (173 hom., cov: 27)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 11 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.274-57009C>T		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.274-57009C>T		intron_variant	Intron 1 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 4629 AN: 136206 Hom.: 174 Cov.: 27

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.00647

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0400

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

GnomAD4 genome AF: 0.0339 AC: 4626 AN: 136296 Hom.: 173 Cov.: 27 AF XY: 0.0386 AC XY: 2521 AN XY: 65358

African (AFR) AF: 0.00803 AC: 280 AN: 34850

American (AMR) AF: 0.0960 AC: 1213 AN: 12630

Ashkenazi Jewish (ASJ) AF: 0.00647 AC: 22 AN: 3398

East Asian (EAS) AF: 0.194 AC: 903 AN: 4664

South Asian (SAS) AF: 0.0854 AC: 357 AN: 4180

European-Finnish (FIN) AF: 0.0202 AC: 160 AN: 7936

Middle Eastern (MID) AF: 0.00400 AC: 1 AN: 250

European-Non Finnish (NFE) AF: 0.0246 AC: 1616 AN: 65646

Other (OTH) AF: 0.0397 AC: 74 AN: 1866

Alfa AF: 0.0275 Hom.: 18

Bravo AF: 0.0355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.1
DANN	Benign	0.93
PhyloP100		-0.10
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: rs11216230; hg19: chr11-116884789;