rs7928320

Variant names:

• chr11-117072037-C-G
• rs7928320
• NM_001366686.3:c.273+26106G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-117072037-C-G
• chr11-117072037-C-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.273+26106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 151,970 control chromosomes in the GnomAD database, including 494 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 0.073 (494 hom., cov: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• 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):

• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.273+26106G>C		intron_variant	Intron 1 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.273+26106G>C		intron_variant	Intron 1 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11062 AN: 151850 Hom.: 492 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0588

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

GnomAD4 genome AF: 0.0728 AC: 11060 AN: 151970 Hom.: 494 Cov.: 31 AF XY: 0.0730 AC XY: 5425 AN XY: 74286

African (AFR) AF: 0.109 AC: 4520 AN: 41442

American (AMR) AF: 0.0393 AC: 600 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3470

East Asian (EAS) AF: 0.0899 AC: 463 AN: 5150

South Asian (SAS) AF: 0.0793 AC: 381 AN: 4806

European-Finnish (FIN) AF: 0.0744 AC: 784 AN: 10532

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3834 AN: 67980

Other (OTH) AF: 0.0577 AC: 122 AN: 2114

Alfa AF: 0.00376 Hom.: 1702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.028
DANN	Benign	0.33
PhyloP100		-2.5
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: rs7928320; hg19: chr11-116942753;