rs625145

chr11-116857220-A-T

Variant summary

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

The NM_001366686.3(SIK3):c.3655+590T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 153,568 control chromosomes in the GnomAD database, including 9,497 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 0.31 (9463 hom., cov: 32)
  • Exomes 𝑓: 0.18 (34 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.3655+590T>A		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.3655+590T>A		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46998 AN: 151976 Hom.: 9437 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.178 AC: 263 AN: 1474 Hom.: 34 Cov.: 0 AF XY: 0.171 AC XY: 131 AN XY: 764

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.0769

GnomAD4 genome AF: 0.310 AC: 47083 AN: 152094 Hom.: 9463 Cov.: 32 AF XY: 0.309 AC XY: 22968 AN XY: 74362

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.275

Alfa AF: 0.273 Hom.: 892

Bravo AF: 0.324

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.14
Dann	Benign	0.44

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: rs625145; hg19: chr11-116727936;