rs10892044

Variant names:

• chr11-116896183-T-C
• rs10892044
• NM_001366686.3:c.865+70A>G

Variant summary

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

The NM_001366686.3(SIK3):​c.865+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,585,922 control chromosomes in the GnomAD database, including 17,944 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 0.16 (2021 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15923 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.865+70A>G		intron_variant	Intron 6 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.865+70A>G		intron_variant	Intron 6 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24105 AN: 152076 Hom.: 2012 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.145 AC: 208345 AN: 1433728 Hom.: 15923 AF XY: 0.146 AC XY: 103718 AN XY: 710286

African (AFR) AF: 0.183 AC: 6009 AN: 32908

American (AMR) AF: 0.215 AC: 9404 AN: 43716

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3421 AN: 25114

East Asian (EAS) AF: 0.0505 AC: 1962 AN: 38822

South Asian (SAS) AF: 0.166 AC: 14012 AN: 84220

European-Finnish (FIN) AF: 0.169 AC: 8828 AN: 52162

Middle Eastern (MID) AF: 0.162 AC: 897 AN: 5554

European-Non Finnish (NFE) AF: 0.142 AC: 155519 AN: 1092326

Other (OTH) AF: 0.141 AC: 8293 AN: 58906

GnomAD4 genome AF: 0.159 AC: 24155 AN: 152194 Hom.: 2021 Cov.: 32 AF XY: 0.159 AC XY: 11836 AN XY: 74404

African (AFR) AF: 0.184 AC: 7640 AN: 41548

American (AMR) AF: 0.176 AC: 2692 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3466

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5178

South Asian (SAS) AF: 0.161 AC: 778 AN: 4828

European-Finnish (FIN) AF: 0.173 AC: 1830 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9983 AN: 67974

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.155 Hom.: 1085

Bravo AF: 0.162

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.17
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: rs10892044; hg19: chr11-116766899; COSMIC: COSV52620697;