dbSNP rs10892044: SIK3:c.865+70A>G (chr11-116896183-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001366686.3(SIK3):c.865+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,585,922 control chromosomes in the GnomAD database, including 17,944 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 ( 2021 hom., cov: 32)

Exomes 𝑓: 0.15 ( 15923 hom. )

Consequence

SIK3
NM_001366686.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165

Publications

10 publications found

Variant links:

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):

spondyloepimetaphyseal dysplasia, Krakow type
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
autism
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hearing loss disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SIK3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001366686.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIK3	NM_001366686.3	MANE Select	c.865+70A>G	intron	N/A	NP_001353615.1	H0Y4E8
SIK3	NM_025164.6		c.865+70A>G	intron	N/A	NP_079440.3
SIK3	NM_001281749.3		c.865+70A>G	intron	N/A	NP_001268678.1	Q9Y2K2-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIK3	ENST00000445177.6	TSL:5 MANE Select	c.865+70A>G	intron	N/A	ENSP00000391295.2	H0Y4E8
SIK3	ENST00000446921.6	TSL:1	c.865+70A>G	intron	N/A	ENSP00000390442.2	Q9Y2K2-8
SIK3	ENST00000415541.5	TSL:1	n.*389+70A>G	intron	N/A	ENSP00000392761.1	H7C038

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24105

AN:

152076

Hom.:

2012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.0497

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.145

AC:

208345

AN:

1433728

Hom.:

15923

AF XY:

0.146

AC XY:

103718

AN XY:

710286

show subpopulations

African (AFR)

AF:

0.183

AC:

6009

AN:

32908

American (AMR)

AF:

0.215

AC:

9404

AN:

43716

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3421

AN:

25114

East Asian (EAS)

AF:

0.0505

AC:

1962

AN:

38822

South Asian (SAS)

AF:

0.166

AC:

14012

AN:

84220

European-Finnish (FIN)

AF:

0.169

AC:

8828

AN:

52162

Middle Eastern (MID)

AF:

0.162

AC:

897

AN:

5554

European-Non Finnish (NFE)

AF:

0.142

AC:

155519

AN:

1092326

Other (OTH)

AF:

0.141

AC:

8293

AN:

58906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8883

17765

26648

35530

44413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5622

11244

16866

22488

28110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.159

AC:

24155

AN:

152194

Hom.:

2021

Cov.:

AF XY:

0.159

AC XY:

11836

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.184

AC:

7640

AN:

41548

American (AMR)

AF:

0.176

AC:

2692

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

463

AN:

3466

East Asian (EAS)

AF:

0.0500

AC:

259

AN:

5178

South Asian (SAS)

AF:

0.161

AC:

778

AN:

4828

European-Finnish (FIN)

AF:

0.173

AC:

1830

AN:

10594

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9983

AN:

67974

Other (OTH)

AF:

0.156

AC:

330

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1044

2088

3131

4175

5219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.155

Hom.:

1085

Bravo

AF:

0.162

Asia WGS

AF:

0.118

AC:

410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.66

PhyloP100

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over