rs2075292

Variant names:

• chr11-116861796-G-A
• rs2075292
• NM_001366686.3:c.2315+45C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-116861796-G-A
• chr11-116861796-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366686.3(SIK3):​c.2315+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 54 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.2315+45C>T		intron	N/A	NP_001353615.1
	SIK3	NM_025164.6		c.2171+45C>T		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.2171+45C>T		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.2315+45C>T		intron	N/A	ENSP00000391295.2
	SIK3	ENST00000446921.6	TSL:1	c.2171+45C>T		intron	N/A	ENSP00000390442.2
	SIK3	ENST00000415541.5	TSL:1	n.*1695+45C>T		intron	N/A	ENSP00000392761.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1159404 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 587840

African (AFR) AF: 0.00 AC: 0 AN: 27446

American (AMR) AF: 0.00 AC: 0 AN: 40828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23674

East Asian (EAS) AF: 0.00 AC: 0 AN: 37852

South Asian (SAS) AF: 0.00 AC: 0 AN: 77034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 845144

Other (OTH) AF: 0.00 AC: 0 AN: 50528

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.85
PhyloP100		-0.57

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: rs2075292; hg19: chr11-116732512;