rs499910

Variant names:

• chr11-116892318-G-A
• rs499910
• NM_001366686.3:c.865+3935C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-116892318-G-A
• chr11-116892318-G-C
• chr11-116892318-G-T

Variant summary

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

The NM_001366686.3(SIK3):​c.865+3935C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,872 control chromosomes in the GnomAD database, including 31,449 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 0.61 (31449 hom., cov: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• 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)

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 = 0.775 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.865+3935C>T		intron	N/A	NP_001353615.1
	SIK3	NM_025164.6		c.865+3935C>T		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.865+3935C>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.865+3935C>T		intron	N/A	ENSP00000391295.2
	SIK3	ENST00000446921.6	TSL:1	c.865+3935C>T		intron	N/A	ENSP00000390442.2
	SIK3	ENST00000415541.5	TSL:1	n.*389+3935C>T		intron	N/A	ENSP00000392761.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92888 AN: 151752 Hom.: 31443 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.612 AC: 92931 AN: 151872 Hom.: 31449 Cov.: 31 AF XY: 0.604 AC XY: 44805 AN XY: 74236

African (AFR) AF: 0.348 AC: 14392 AN: 41374

American (AMR) AF: 0.638 AC: 9748 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1374 AN: 5142

South Asian (SAS) AF: 0.449 AC: 2161 AN: 4818

European-Finnish (FIN) AF: 0.709 AC: 7473 AN: 10534

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53025 AN: 67950

Other (OTH) AF: 0.644 AC: 1358 AN: 2110

Alfa AF: 0.695 Hom.: 16951

Bravo AF: 0.599

Asia WGS AF: 0.336 AC: 1171 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	0.44
DANN	Benign	0.68
PhyloP100		-1.8
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: rs499910; hg19: chr11-116763034;