11-117044304-T-C

Position:

• chr11-117044304-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.273+53839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,148 control chromosomes in the GnomAD database, including 2,125 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 0.16 (2125 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.273+53839A>G		intron_variant		ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.273+53839A>G		intron_variant		5	NM_001366686.3	ENSP00000391295	A2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24655 AN: 152028 Hom.: 2115 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.162 AC: 24711 AN: 152148 Hom.: 2125 Cov.: 32 AF XY: 0.164 AC XY: 12216 AN XY: 74378

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0535

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.160

Alfa AF: 0.158 Hom.: 254

Bravo AF: 0.168

Asia WGS AF: 0.124 AC: 428 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.85

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: rs17120241; hg19: chr11-116915020;