chr11-116943263-A-G

Variant names:

• chr11-116943263-A-G
• rs12292858
• NM_001366686.3:c.454+10781T>C

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.454+10781T>C 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: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 10 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

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=-0.76).

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.454+10781T>C		intron	N/A	NP_001353615.1	H0Y4E8
	SIK3	NM_025164.6		c.454+10781T>C		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.454+10781T>C		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.454+10781T>C		intron	N/A	ENSP00000391295.2	H0Y4E8
	SIK3	ENST00000446921.6	TSL:1	c.454+10781T>C		intron	N/A	ENSP00000390442.2	Q9Y2K2-8
	SIK3	ENST00000415541.5	TSL:1	n.434+6870T>C		intron	N/A	ENSP00000392761.1	H7C038

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.81
PhyloP100		0.28

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: rs12292858; hg19: chr11-116813979;