rs10047459

Positions:

• chr11-116851110-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.3656-1827G>A		intron_variant		ENST00000445177.6	NP_001353615.1
APOA1-AS	NR_126362.1	n.124-4180C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.3656-1827G>A		intron_variant		5	NM_001366686.3	ENSP00000391295	A2
APOA1-AS	ENST00000669664.1	n.75-2760C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.793

Alfa AF: 0.820 Hom.: 103874

Bravo AF: 0.792

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.55

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: rs10047459; hg19: chr11-116721826;