chr11-116859922-A-G

Variant summary

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

The NM_001366686.3(SIK3):​c.2426-318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,200 control chromosomes in the GnomAD database, including 60,597 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 0.89 ( 60597 hom., cov: 31)

Consequence

SIK3
NM_001366686.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.834

Publications

11 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)

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=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIK3NM_001366686.3 linkc.2426-318T>C intron_variant Intron 19 of 24 ENST00000445177.6 NP_001353615.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIK3ENST00000445177.6 linkc.2426-318T>C intron_variant Intron 19 of 24 5 NM_001366686.3 ENSP00000391295.2 H0Y4E8

Frequencies

GnomAD3 genomes
AF:
0.890
AC:
135339
AN:
152082
Hom.:
60556
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.933
Gnomad AMI
AF:
0.987
Gnomad AMR
AF:
0.829
Gnomad ASJ
AF:
0.875
Gnomad EAS
AF:
0.653
Gnomad SAS
AF:
0.735
Gnomad FIN
AF:
0.854
Gnomad MID
AF:
0.870
Gnomad NFE
AF:
0.912
Gnomad OTH
AF:
0.890
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.890
AC:
135436
AN:
152200
Hom.:
60597
Cov.:
31
AF XY:
0.882
AC XY:
65635
AN XY:
74412
show subpopulations
African (AFR)
AF:
0.933
AC:
38760
AN:
41546
American (AMR)
AF:
0.828
AC:
12670
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.875
AC:
3036
AN:
3468
East Asian (EAS)
AF:
0.653
AC:
3375
AN:
5166
South Asian (SAS)
AF:
0.736
AC:
3547
AN:
4820
European-Finnish (FIN)
AF:
0.854
AC:
9042
AN:
10590
Middle Eastern (MID)
AF:
0.871
AC:
256
AN:
294
European-Non Finnish (NFE)
AF:
0.912
AC:
61983
AN:
68000
Other (OTH)
AF:
0.885
AC:
1869
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
718
1437
2155
2874
3592
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
894
1788
2682
3576
4470
<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:
0.907
Hom.:
84332
Bravo
AF:
0.895
Asia WGS
AF:
0.702
AC:
2444
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.026
DANN
Benign
0.35
PhyloP100
-0.83
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

Publications

Other links and lift over

dbSNP: rs6589574; hg19: chr11-116730638; API