rs609177

Variant names:

• chr11-116899801-A-G
• rs609177
• NM_001366686.3:c.617-2484T>C

Variant summary

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

The ENST00000445177.6(SIK3):​c.617-2484T>C 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 151,962 control chromosomes in the GnomAD database, including 18,955 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 (18955 hom., cov: 30)
• Consequence: SIK3 ENST00000445177.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445177.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	NM_001366686.3	MANE Select	c.617-2484T>C		intron	N/A	NP_001353615.1
	SIK3	NM_025164.6		c.617-2484T>C		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.617-2484T>C		intron	N/A	NP_001268678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	ENST00000445177.6	TSL:5 MANE Select	c.617-2484T>C		intron	N/A	ENSP00000391295.2
	SIK3	ENST00000446921.6	TSL:1	c.617-2484T>C		intron	N/A	ENSP00000390442.2
	SIK3	ENST00000415541.5	TSL:1	n.*141-2484T>C		intron	N/A	ENSP00000392761.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68897 AN: 151846 Hom.: 18961 Cov.: 30

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.453 AC: 68886 AN: 151962 Hom.: 18955 Cov.: 30 AF XY: 0.445 AC XY: 33041 AN XY: 74256

African (AFR) AF: 0.161 AC: 6687 AN: 41476

American (AMR) AF: 0.462 AC: 7059 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1181 AN: 5164

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4810

European-Finnish (FIN) AF: 0.536 AC: 5639 AN: 10520

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43077 AN: 67950

Other (OTH) AF: 0.487 AC: 1021 AN: 2098

Alfa AF: 0.508 Hom.: 2879

Bravo AF: 0.438

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.6
DANN	Benign	0.62
PhyloP100		-0.081
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: rs609177; hg19: chr11-116770517;