11-116863829-G-A

Variant names:

• chr11-116863829-G-A
• rs11216164
• NM_001366686.3:c.1953-11C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_001366686.3(SIK3):​c.1953-11C>T variant causes a intron change. The variant allele was found at a frequency of 0.287 in 1,590,200 control chromosomes in the GnomAD database, including 73,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4819 hom., cov: 32)
  • Exomes 𝑓: 0.29 (68285 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Scores: Splicing: ADA: 0.9384
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.95
• Publications: 21 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 11-116863829-G-A is Benign according to our data. Variant chr11-116863829-G-A is described in ClinVar as Benign. ClinVar VariationId is 1332966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 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.1953-11C>T		intron	N/A	NP_001353615.1	H0Y4E8
	SIK3	NM_025164.6		c.1809-11C>T		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.1809-11C>T		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.1953-11C>T		intron	N/A	ENSP00000391295.2	H0Y4E8
	SIK3	ENST00000446921.6	TSL:1	c.1809-11C>T		intron	N/A	ENSP00000390442.2	Q9Y2K2-8
	SIK3	ENST00000415541.5	TSL:1	n.*1333-11C>T		intron	N/A	ENSP00000392761.1	H7C038

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33243 AN: 152038 Hom.: 4821 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.232 AC: 53913 AN: 232600 AF XY: 0.236

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.0224

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.295 AC: 423545 AN: 1438044 Hom.: 68285 Cov.: 32 AF XY: 0.290 AC XY: 206468 AN XY: 712986

African (AFR) AF: 0.0520 AC: 1705 AN: 32772

American (AMR) AF: 0.168 AC: 7152 AN: 42474

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5572 AN: 24684

East Asian (EAS) AF: 0.0190 AC: 744 AN: 39180

South Asian (SAS) AF: 0.0931 AC: 7752 AN: 83234

European-Finnish (FIN) AF: 0.289 AC: 15213 AN: 52628

Middle Eastern (MID) AF: 0.221 AC: 1246 AN: 5640

European-Non Finnish (NFE) AF: 0.335 AC: 368376 AN: 1098248

Other (OTH) AF: 0.267 AC: 15785 AN: 59184

GnomAD4 genome AF: 0.218 AC: 33238 AN: 152156 Hom.: 4819 Cov.: 32 AF XY: 0.210 AC XY: 15593 AN XY: 74368

African (AFR) AF: 0.0623 AC: 2589 AN: 41534

American (AMR) AF: 0.205 AC: 3134 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3472

East Asian (EAS) AF: 0.0252 AC: 130 AN: 5168

South Asian (SAS) AF: 0.0854 AC: 412 AN: 4826

European-Finnish (FIN) AF: 0.281 AC: 2975 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22312 AN: 67966

Other (OTH) AF: 0.241 AC: 507 AN: 2104

Alfa AF: 0.286 Hom.: 10103

Bravo AF: 0.211

Asia WGS AF: 0.0550 AC: 194 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	-0.18
CADD	Benign	22
DANN	Benign	0.84
PhyloP100		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Benign	0.71
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: rs11216164; hg19: chr11-116734545;