rs11216162

Variant names:

• chr11-116857561-G-A
• rs11216162
• ENST00000480468.1:n.1590C>T

Variant summary

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

The ENST00000480468.1(SIK3):​n.1590C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 536,616 control chromosomes in the GnomAD database, including 8,243 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 0.17 (2323 hom., cov: 32)
  • Exomes 𝑓: 0.17 (5920 hom.)
• Consequence: SIK3 ENST00000480468.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.3655+249C>T		intron_variant	Intron 21 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.3655+249C>T		intron_variant	Intron 21 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25893 AN: 152058 Hom.: 2316 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.170 AC: 65435 AN: 384442 Hom.: 5920 Cov.: 6 AF XY: 0.173 AC XY: 34142 AN XY: 197806

African (AFR) AF: 0.135 AC: 1483 AN: 10966

American (AMR) AF: 0.203 AC: 2083 AN: 10284

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 1751 AN: 11292

East Asian (EAS) AF: 0.0847 AC: 1991 AN: 23520

South Asian (SAS) AF: 0.232 AC: 6494 AN: 27952

European-Finnish (FIN) AF: 0.181 AC: 3837 AN: 21162

Middle Eastern (MID) AF: 0.147 AC: 249 AN: 1690

European-Non Finnish (NFE) AF: 0.172 AC: 43886 AN: 255828

Other (OTH) AF: 0.168 AC: 3661 AN: 21748

GnomAD4 genome AF: 0.170 AC: 25936 AN: 152174 Hom.: 2323 Cov.: 32 AF XY: 0.172 AC XY: 12823 AN XY: 74388

African (AFR) AF: 0.144 AC: 5961 AN: 41500

American (AMR) AF: 0.185 AC: 2837 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3472

East Asian (EAS) AF: 0.0941 AC: 488 AN: 5188

South Asian (SAS) AF: 0.261 AC: 1258 AN: 4820

European-Finnish (FIN) AF: 0.191 AC: 2025 AN: 10584

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12317 AN: 67996

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.180 Hom.: 4368

Bravo AF: 0.167

Asia WGS AF: 0.191 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.21
PhyloP100		0.018
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: rs11216162; hg19: chr11-116728277;