NM_001366686.3:c.273+26106G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366686.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	NM_001366686.3	MANE Select	c.273+26106G>A		intron	N/A	NP_001353615.1
	SIK3	NM_025164.6		c.273+26106G>A		intron	N/A	NP_079440.3
	SIK3	NM_001281749.3		c.273+26106G>A		intron	N/A	NP_001268678.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK3	ENST00000445177.6	TSL:5 MANE Select	c.273+26106G>A		intron	N/A	ENSP00000391295.2
	SIK3	ENST00000446921.6	TSL:1	c.273+26106G>A		intron	N/A	ENSP00000390442.2
	SIK3	ENST00000415541.5	TSL:1	n.129+26106G>A		intron	N/A	ENSP00000392761.1

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

African (AFR) AF: 0.606 AC: 25122 AN: 41432

American (AMR) AF: 0.287 AC: 4374 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3468

East Asian (EAS) AF: 0.177 AC: 912 AN: 5146

South Asian (SAS) AF: 0.297 AC: 1425 AN: 4806

European-Finnish (FIN) AF: 0.213 AC: 2246 AN: 10534

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13089 AN: 67980

Other (OTH) AF: 0.290 AC: 613 AN: 2112

Alfa AF: 0.201 Hom.: 1702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.033
DANN	Benign	0.35
PhyloP100		-2.5
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: rs7928320; hg19: chr11-116942753;