rs12099358

Positions:

• chr11-116855332-C-A
• chr11-116855332-C-G

Variant summary

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

The NM_001366686.3(SIK3):​c.3655+2478G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,014 control chromosomes in the GnomAD database, including 5,423 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 0.23 (5423 hom., cov: 31)
  • Exomes 𝑓: 0.078 (0 hom.)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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]

APOA1-AS (HGNC:40079): (APOA1 antisense RNA)

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 = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.3655+2478G>T		intron_variant		ENST00000445177.6	NP_001353615.1
APOA1-AS	NR_126362.1	n.166C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.3655+2478G>T		intron_variant		5	NM_001366686.3	ENSP00000391295	A2
APOA1-AS	ENST00000669664.1	n.270C>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35633 AN: 151832 Hom.: 5402 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.0781 AC: 5 AN: 64 Hom.: 0 Cov.: 0 AF XY: 0.0690 AC XY: 4 AN XY: 58

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.235 AC: 35706 AN: 151950 Hom.: 5423 Cov.: 31 AF XY: 0.233 AC XY: 17292 AN XY: 74236

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.205

Alfa AF: 0.181 Hom.: 630

Bravo AF: 0.248

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.54

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: rs12099358; hg19: chr11-116726048;