dbSNP rs625145: SIK3:n.1931T>A (chr11-116857220-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000480468.1(SIK3):n.1931T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 153,568 control chromosomes in the GnomAD database, including 9,497 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 0.31 ( 9463 hom., cov: 32)

Exomes 𝑓: 0.18 ( 34 hom. )

Consequence

SIK3
ENST00000480468.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.439

Publications

16 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):

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)

SIK3 links:

Genome browser will be placed here

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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000480468.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIK3	NM_001366686.3	MANE Select	c.3655+590T>A	intron	N/A	NP_001353615.1
SIK3	NM_025164.6		c.3511+590T>A	intron	N/A	NP_079440.3
SIK3	NM_001281749.3		c.3331+590T>A	intron	N/A	NP_001268678.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIK3	ENST00000480468.1	TSL:1	n.1931T>A	non_coding_transcript_exon	Exon 3 of 3
SIK3	ENST00000445177.6	TSL:5 MANE Select	c.3655+590T>A	intron	N/A	ENSP00000391295.2
SIK3	ENST00000446921.6	TSL:1	c.3331+590T>A	intron	N/A	ENSP00000390442.2

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46998

AN:

151976

Hom.:

9437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.578

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.276

GnomAD4 exome

AF:

0.178

AC:

263

AN:

1474

Hom.:

Cov.:

AF XY:

0.171

AC XY:

131

AN XY:

764

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.236

AC:

AN:

292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.287

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.158

AC:

162

AN:

1026

Other (OTH)

AF:

0.0769

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.310

AC:

47083

AN:

152094

Hom.:

9463

Cov.:

AF XY:

0.309

AC XY:

22968

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.578

AC:

23959

AN:

41440

American (AMR)

AF:

0.248

AC:

3791

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

599

AN:

3464

East Asian (EAS)

AF:

0.176

AC:

910

AN:

5174

South Asian (SAS)

AF:

0.286

AC:

1379

AN:

4822

European-Finnish (FIN)

AF:

0.203

AC:

2153

AN:

10590

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13529

AN:

67988

Other (OTH)

AF:

0.275

AC:

582

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1437

2874

4311

5748

7185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.273

Hom.:

892

Bravo

AF:

0.324

Asia WGS

AF:

0.276

AC:

958

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.14

(source)

DANN

Benign

0.44

PhyloP100

-0.44

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

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