chr11-117044304-T-C

Variant names:

• chr11-117044304-T-C
• rs17120241
• NM_001366686.3:c.273+53839A>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.273+53839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,148 control chromosomes in the GnomAD database, including 2,125 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 (2125 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	NM_001366686.3	MANE Select	c.273+53839A>G		intron	N/A	NP_001353615.1
	SIK3	NM_025164.6		c.273+53839A>G		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.273+53839A>G		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.273+53839A>G		intron	N/A	ENSP00000391295.2
	SIK3	ENST00000446921.6	TSL:1	c.273+53839A>G		intron	N/A	ENSP00000390442.2
	SIK3	ENST00000415541.5	TSL:1	n.129+53839A>G		intron	N/A	ENSP00000392761.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24655 AN: 152028 Hom.: 2115 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.162 AC: 24711 AN: 152148 Hom.: 2125 Cov.: 32 AF XY: 0.164 AC XY: 12216 AN XY: 74378

African (AFR) AF: 0.190 AC: 7879 AN: 41506

American (AMR) AF: 0.211 AC: 3222 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3466

East Asian (EAS) AF: 0.0535 AC: 278 AN: 5192

South Asian (SAS) AF: 0.161 AC: 777 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1946 AN: 10582

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9616 AN: 67980

Other (OTH) AF: 0.160 AC: 337 AN: 2110

Alfa AF: 0.158 Hom.: 264

Bravo AF: 0.168

Asia WGS AF: 0.124 AC: 428 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		0.036
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: rs17120241; hg19: chr11-116915020;