rs1473177

Positions:

• chr11-116888616-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366686.3(SIK3):​c.865+7637A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,336 control chromosomes in the GnomAD database, including 770 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 0.089 (770 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.865+7637A>G		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.865+7637A>G		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13581 AN: 152218 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0892 AC: 13593 AN: 152336 Hom.: 770 Cov.: 32 AF XY: 0.0901 AC XY: 6711 AN XY: 74484

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.0501

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0889

Alfa AF: 0.109 Hom.: 943

Bravo AF: 0.0880

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.60

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: rs1473177; hg19: chr11-116759332;