chr11-116846420-G-A

Variant names:

• chr11-116846420-G-A
• rs150767868
• NM_001366686.3:c.4086C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001366686.3(SIK3):​c.4086C>T​(p.Phe1362Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00346 in 1,614,190 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (12 hom.)
• Consequence: SIK3 NM_001366686.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.84
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 11-116846420-G-A is Benign according to our data. Variant chr11-116846420-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR,AD,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.4086C>T	p.Phe1362Phe	synonymous_variant	Exon 24 of 25	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.4086C>T	p.Phe1362Phe	synonymous_variant	Exon 24 of 25	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152216 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00306 AC: 770 AN: 251436 AF XY: 0.00331

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00615

Gnomad NFE exome AF: 0.00471

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00357 AC: 5222 AN: 1461856 Hom.: 12 Cov.: 31 AF XY: 0.00361 AC XY: 2624 AN XY: 727224

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00231 AC: 199 AN: 86256

European-Finnish (FIN) AF: 0.00841 AC: 449 AN: 53420

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5744

European-Non Finnish (NFE) AF: 0.00393 AC: 4370 AN: 1112004

Other (OTH) AF: 0.00270 AC: 163 AN: 60392

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152334 Hom.: 1 Cov.: 32 AF XY: 0.00242 AC XY: 180 AN XY: 74504

African (AFR) AF: 0.000602 AC: 25 AN: 41556

American (AMR) AF: 0.000392 AC: 6 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4830

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00382 AC: 260 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00364 Hom.: 1

Bravo AF: 0.00208

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00308

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

SIK3-related disorder Benign:1

Apr 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

APOA1-AS: BS2; SIK3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		3.8
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -37

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150767868; hg19: chr11-116717136; COSMIC: COSV109417737;