rs12099358

Variant names:

• chr11-116855332-C-A
• rs12099358
• NM_001366686.3:c.3655+2478G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.3655+2478G>T		intron_variant	Intron 21 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.3655+2478G>T		intron_variant	Intron 21 of 24	5	NM_001366686.3	ENSP00000391295.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 5 AN: 50

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.442 AC: 18273 AN: 41358

American (AMR) AF: 0.204 AC: 3113 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3470

East Asian (EAS) AF: 0.0502 AC: 259 AN: 5158

South Asian (SAS) AF: 0.148 AC: 712 AN: 4812

European-Finnish (FIN) AF: 0.183 AC: 1933 AN: 10556

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10352 AN: 67998

Other (OTH) AF: 0.205 AC: 432 AN: 2112

Alfa AF: 0.188 Hom.: 701

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12099358; hg19: chr11-116726048;