rs687172

chr11-116860544-T-A

Variant summary

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

The NM_001366686.3(SIK3):c.2425+730A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,150 control chromosomes in the GnomAD database, including 5,081 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 0.17 (5081 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK3	NM_001366686.3	c.2425+730A>T		intron_variant		ENST00000445177.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK3	ENST00000445177.6	c.2425+730A>T		intron_variant		5	NM_001366686.3	A2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26549 AN: 152032 Hom.: 5073 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.175 AC: 26589 AN: 152150 Hom.: 5081 Cov.: 32 AF XY: 0.174 AC XY: 12918 AN XY: 74388

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0294

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.136

Alfa AF: 0.126 Hom.: 362

Bravo AF: 0.191

Asia WGS AF: 0.175 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.44

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: rs687172; hg19: chr11-116731260;