chr11-116958937-T-G

Position:

• chr11-116958937-T-G

Variant summary

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

The NM_001366686.3(SIK3):​c.274-1873A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,200 control chromosomes in the GnomAD database, including 2,469 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 (2469 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.274-1873A>C		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.274-1873A>C		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23768 AN: 152082 Hom.: 2471 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.156 AC: 23760 AN: 152200 Hom.: 2469 Cov.: 32 AF XY: 0.153 AC XY: 11396 AN XY: 74408

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.164

Alfa AF: 0.193 Hom.: 2333

Bravo AF: 0.145

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.64

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: rs7120173; hg19: chr11-116829653;