11-116958937-T-G

Variant names:

• chr11-116958937-T-G
• rs7120173
• NM_001366686.3:c.274-1873A>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.274-1873A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,200 control chromosomes in the GnomAD database, including 2,469 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 0.16 (2469 hom., cov: 32)
• Consequence: SIK3 NM_001366686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.274-1873A>C		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.274-1873A>C		intron_variant	Intron 1 of 24	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23768 AN: 152082 Hom.: 2471 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.156 AC: 23760 AN: 152200 Hom.: 2469 Cov.: 32 AF XY: 0.153 AC XY: 11396 AN XY: 74408

African (AFR) AF: 0.0424 AC: 1762 AN: 41544

American (AMR) AF: 0.130 AC: 1985 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5180

South Asian (SAS) AF: 0.125 AC: 603 AN: 4832

European-Finnish (FIN) AF: 0.195 AC: 2061 AN: 10588

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15707 AN: 67986

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.178 Hom.: 3708

Bravo AF: 0.145

Asia WGS AF: 0.0570 AC: 198 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	3.8
DANN	Benign	0.64
PhyloP100		1.2
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: rs7120173; hg19: chr11-116829653;