chr11-116865963-A-G

Variant names:

• chr11-116865963-A-G
• rs573549
• NM_001366686.3:c.1952+1983T>C

Variant summary

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

The NM_001366686.3(SIK3):​c.1952+1983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,996 control chromosomes in the GnomAD database, including 19,073 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 0.46 (19073 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.1952+1983T>C		intron_variant	Intron 15 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.1952+1983T>C		intron_variant	Intron 15 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69937 AN: 151878 Hom.: 19077 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.460 AC: 69932 AN: 151996 Hom.: 19073 Cov.: 32 AF XY: 0.452 AC XY: 33583 AN XY: 74300

African (AFR) AF: 0.193 AC: 8006 AN: 41480

American (AMR) AF: 0.463 AC: 7062 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1883 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1192 AN: 5180

South Asian (SAS) AF: 0.313 AC: 1505 AN: 4814

European-Finnish (FIN) AF: 0.534 AC: 5631 AN: 10554

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42760 AN: 67928

Other (OTH) AF: 0.489 AC: 1030 AN: 2108

Alfa AF: 0.564 Hom.: 69024

Bravo AF: 0.446

Asia WGS AF: 0.233 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		0.96
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: rs573549; hg19: chr11-116736679;