11-117072037-C-T

Variant names:

• chr11-117072037-C-T
• rs7928320
• NM_001366686.3:c.273+26106G>A

Variant summary

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

The NM_001366686.3(SIK3):​c.273+26106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,942 control chromosomes in the GnomAD database, including 10,219 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 0.32 (10219 hom., cov: 31)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.273+26106G>A		intron_variant	Intron 1 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.273+26106G>A		intron_variant	Intron 1 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48547 AN: 151822 Hom.: 10187 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.320 AC: 48639 AN: 151942 Hom.: 10219 Cov.: 31 AF XY: 0.321 AC XY: 23826 AN XY: 74274

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.290

Alfa AF: 0.200 Hom.: 1529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.033
DANN	Benign	0.35

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: rs7928320; hg19: chr11-116942753;