rs482371

Variant names:

• chr11-116881447-T-C
• rs482371
• NM_001366686.3:c.866-4405A>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.866-4405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,162 control chromosomes in the GnomAD database, including 18,900 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 0.45 (18900 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883
• Publications: 11 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

ENSG00000296731 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 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.866-4405A>G		intron	N/A	NP_001353615.1	H0Y4E8
	SIK3	NM_025164.6		c.866-4405A>G		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.866-4405A>G		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.866-4405A>G		intron	N/A	ENSP00000391295.2	H0Y4E8
	SIK3	ENST00000446921.6	TSL:1	c.866-4405A>G		intron	N/A	ENSP00000390442.2	Q9Y2K2-8
	SIK3	ENST00000415541.5	TSL:1	n.*390-4405A>G		intron	N/A	ENSP00000392761.1	H7C038

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68950 AN: 152042 Hom.: 18905 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.453 AC: 68938 AN: 152162 Hom.: 18900 Cov.: 32 AF XY: 0.445 AC XY: 33116 AN XY: 74396

African (AFR) AF: 0.165 AC: 6868 AN: 41530

American (AMR) AF: 0.463 AC: 7072 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1887 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1115 AN: 5172

South Asian (SAS) AF: 0.302 AC: 1457 AN: 4824

European-Finnish (FIN) AF: 0.535 AC: 5665 AN: 10582

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42954 AN: 67986

Other (OTH) AF: 0.490 AC: 1032 AN: 2108

Alfa AF: 0.562 Hom.: 20174

Bravo AF: 0.438

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.61
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs482371; hg19: chr11-116752163;