11-116851325-G-T

Variant names:

• chr11-116851325-G-T
• rs10047462
• NM_001366686.3:c.3656-2042C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366686.3(SIK3):​c.3656-2042C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,202 control chromosomes in the GnomAD database, including 57,767 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 0.87 (57767 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 23 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 = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.3656-2042C>A		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.3656-2042C>A		intron_variant	Intron 21 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131684 AN: 152084 Hom.: 57729 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.866 AC: 131769 AN: 152202 Hom.: 57767 Cov.: 32 AF XY: 0.856 AC XY: 63664 AN XY: 74402

African (AFR) AF: 0.925 AC: 38417 AN: 41534

American (AMR) AF: 0.776 AC: 11872 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3047 AN: 3472

East Asian (EAS) AF: 0.483 AC: 2493 AN: 5164

South Asian (SAS) AF: 0.674 AC: 3248 AN: 4816

European-Finnish (FIN) AF: 0.825 AC: 8740 AN: 10588

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 61007 AN: 68012

Other (OTH) AF: 0.853 AC: 1804 AN: 2114

Alfa AF: 0.876 Hom.: 206089

Bravo AF: 0.868

Asia WGS AF: 0.601 AC: 2096 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	0.016
DANN	Benign	0.23
PhyloP100		-2.0
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: rs10047462; hg19: chr11-116722041;