chr11-116912258-T-G

Variant names:

• chr11-116912258-T-G
• rs11216185
• NM_001366686.3:c.617-14941A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366686.3(SIK3):​c.617-14941A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 152,228 control chromosomes in the GnomAD database, including 503 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 0.074 (503 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954
• Publications: 15 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]

SIK3 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• spondyloepimetaphyseal dysplasia, Krakow type

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.617-14941A>C		intron_variant	Intron 4 of 24	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.617-14941A>C		intron_variant	Intron 4 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11297 AN: 152110 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0590

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

GnomAD4 genome AF: 0.0742 AC: 11289 AN: 152228 Hom.: 503 Cov.: 32 AF XY: 0.0741 AC XY: 5512 AN XY: 74416

African (AFR) AF: 0.110 AC: 4550 AN: 41526

American (AMR) AF: 0.0402 AC: 614 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3472

East Asian (EAS) AF: 0.0789 AC: 409 AN: 5186

South Asian (SAS) AF: 0.0802 AC: 387 AN: 4828

European-Finnish (FIN) AF: 0.0737 AC: 781 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0593 AC: 4034 AN: 68020

Other (OTH) AF: 0.0579 AC: 122 AN: 2106

Alfa AF: 0.0640 Hom.: 1487

Bravo AF: 0.0746

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.95
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: rs11216185; hg19: chr11-116782974;