rs7928320

Positions:

• chr11-117072037-C-G
• chr11-117072037-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SIK3	NM_001366686.3	c.273+26106G>C		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.273+26106G>C		intron_variant		5	NM_001366686.3	A2

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0393

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0899

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.00422 Hom.: 1529

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7928320; hg19: chr11-116942753;