rs2075292

Variant names:

• chr11-116861796-G-T
• rs2075292
• NM_001366686.3:c.2315+45C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-116861796-G-T
• chr11-116861796-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366686.3(SIK3):​c.2315+45C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,310,282 control chromosomes in the GnomAD database, including 480,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (56248 hom., cov: 32)
  • Exomes 𝑓: 0.85 (423902 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.575
• Publications: 54 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):

• spondyloepimetaphyseal dysplasia, Krakow type

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• autism

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-116861796-G-T is Benign according to our data. Variant chr11-116861796-G-T is described in ClinVar as Benign. ClinVar VariationId is 1332965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366686.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	NM_001366686.3	MANE Select	c.2315+45C>A		intron	N/A	NP_001353615.1	H0Y4E8
	SIK3	NM_025164.6		c.2171+45C>A		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.2171+45C>A		intron	N/A	NP_001268678.1	Q9Y2K2-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	ENST00000445177.6	TSL:5 MANE Select	c.2315+45C>A		intron	N/A	ENSP00000391295.2	H0Y4E8
	SIK3	ENST00000446921.6	TSL:1	c.2171+45C>A		intron	N/A	ENSP00000390442.2	Q9Y2K2-8
	SIK3	ENST00000415541.5	TSL:1	n.*1695+45C>A		intron	N/A	ENSP00000392761.1	H7C038

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129887 AN: 152024 Hom.: 56211 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.842

GnomAD2 exomes AF: 0.798 AC: 175287 AN: 219536 AF XY: 0.798

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.826

Gnomad EAS exome AF: 0.488

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.850 AC: 984460 AN: 1158140 Hom.: 423902 Cov.: 15 AF XY: 0.845 AC XY: 495982 AN XY: 587218

African (AFR) AF: 0.915 AC: 25090 AN: 27430

American (AMR) AF: 0.714 AC: 29086 AN: 40750

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 19514 AN: 23652

East Asian (EAS) AF: 0.475 AC: 17974 AN: 37828

South Asian (SAS) AF: 0.686 AC: 52778 AN: 76930

European-Finnish (FIN) AF: 0.824 AC: 42613 AN: 51708

Middle Eastern (MID) AF: 0.803 AC: 4138 AN: 5152

European-Non Finnish (NFE) AF: 0.890 AC: 751101 AN: 844206

Other (OTH) AF: 0.835 AC: 42166 AN: 50484

GnomAD4 genome AF: 0.854 AC: 129971 AN: 152142 Hom.: 56248 Cov.: 32 AF XY: 0.844 AC XY: 62767 AN XY: 74358

African (AFR) AF: 0.918 AC: 38126 AN: 41522

American (AMR) AF: 0.756 AC: 11550 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2867 AN: 3472

East Asian (EAS) AF: 0.481 AC: 2479 AN: 5158

South Asian (SAS) AF: 0.671 AC: 3235 AN: 4818

European-Finnish (FIN) AF: 0.812 AC: 8580 AN: 10572

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

European-Non Finnish (NFE) AF: 0.886 AC: 60250 AN: 68012

Other (OTH) AF: 0.833 AC: 1760 AN: 2112

Alfa AF: 0.869 Hom.: 222746

Bravo AF: 0.856

Asia WGS AF: 0.598 AC: 2082 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spondyloepimetaphyseal dysplasia, Krakow type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.40
PhyloP100		-0.57
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: rs2075292; hg19: chr11-116732512; COSMIC: COSV52610391; COSMIC: COSV52610391;