rs2000615

Variant names:

• chr11-117045103-C-T
• rs2000615
• NM_001366686.3:c.273+53040G>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+53040G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,160 control chromosomes in the GnomAD database, including 56,435 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 0.86 (56435 hom., cov: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.273+53040G>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+53040G>A		intron_variant	Intron 1 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130192 AN: 152042 Hom.: 56397 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.856 AC: 130275 AN: 152160 Hom.: 56435 Cov.: 31 AF XY: 0.847 AC XY: 63020 AN XY: 74372

African (AFR) AF: 0.904 AC: 37545 AN: 41512

American (AMR) AF: 0.795 AC: 12159 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2869 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2464 AN: 5156

South Asian (SAS) AF: 0.672 AC: 3237 AN: 4816

European-Finnish (FIN) AF: 0.821 AC: 8683 AN: 10576

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60412 AN: 68030

Other (OTH) AF: 0.839 AC: 1770 AN: 2110

Alfa AF: 0.876 Hom.: 8600

Bravo AF: 0.860

Asia WGS AF: 0.602 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.31
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2000615; hg19: chr11-116915819;