rs10047459

Variant names:

• chr11-116851110-C-T
• rs10047459
• NM_001366686.3:c.3656-1827G>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.3656-1827G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,216 control chromosomes in the GnomAD database, including 48,214 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 0.79 (48214 hom., cov: 34)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366686.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	NM_001366686.3	MANE Select	c.3656-1827G>A		intron	N/A	NP_001353615.1	H0Y4E8
	SIK3	NM_025164.6		c.3512-1827G>A		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.3332-1827G>A		intron	N/A	NP_001268678.1	Q9Y2K2-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	ENST00000445177.6	TSL:5 MANE Select	c.3656-1827G>A		intron	N/A	ENSP00000391295.2	H0Y4E8
	SIK3	ENST00000446921.6	TSL:1	c.3332-1827G>A		intron	N/A	ENSP00000390442.2	Q9Y2K2-8
	SIK3	ENST00000415541.5	TSL:1	n.*2856-1827G>A		intron	N/A	ENSP00000392761.1	H7C038

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120198 AN: 152098 Hom.: 48164 Cov.: 34

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.790 AC: 120293 AN: 152216 Hom.: 48214 Cov.: 34 AF XY: 0.781 AC XY: 58139 AN XY: 74414

African (AFR) AF: 0.812 AC: 33695 AN: 41510

American (AMR) AF: 0.735 AC: 11244 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2710 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2090 AN: 5174

South Asian (SAS) AF: 0.590 AC: 2842 AN: 4820

European-Finnish (FIN) AF: 0.753 AC: 7973 AN: 10590

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56991 AN: 68026

Other (OTH) AF: 0.793 AC: 1676 AN: 2114

Alfa AF: 0.818 Hom.: 214345

Bravo AF: 0.792

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.55
PhyloP100		-0.82
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: rs10047459; hg19: chr11-116721826;