chr21-43417679-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173354.5(SIK1):​c.1840C>G​(p.Gln614Glu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q614H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SIK1
NM_173354.5 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.65

Publications

3 publications found
Variant links:
Genes affected
SIK1 (HGNC:11142): (salt inducible kinase 1) This gene encodes a serine/threonine protein kinase that contains a ubiquitin-associated (UBA) domain. The encoded protein is a member of the adenosine monophosphate-activated kinase (AMPK) subfamily of kinases that play a role in conserved signal transduction pathways. A mutation in this gene is associated with early infantile epileptic encephalopathy 30. [provided by RefSeq, Nov 2016]
SIK1 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 30
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • early myoclonic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • infantile spasms
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • generalized epilepsy
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1765483).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIK1NM_173354.5 linkc.1840C>G p.Gln614Glu missense_variant Exon 13 of 14 ENST00000270162.8 NP_775490.2 P57059
SIK1XM_011529474.3 linkc.1693C>G p.Gln565Glu missense_variant Exon 12 of 13 XP_011527776.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIK1ENST00000270162.8 linkc.1840C>G p.Gln614Glu missense_variant Exon 13 of 14 1 NM_173354.5 ENSP00000270162.6 P57059

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD2 exomes
AF:
0.00000469
AC:
1
AN:
213224
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000187
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
339902
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
168296
African (AFR)
AF:
0.00
AC:
0
AN:
15222
American (AMR)
AF:
0.00
AC:
0
AN:
4136
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
7186
East Asian (EAS)
AF:
0.00
AC:
0
AN:
7556
South Asian (SAS)
AF:
0.00
AC:
0
AN:
21574
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4906
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1234
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
262068
Other (OTH)
AF:
0.00
AC:
0
AN:
16020
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T
Eigen
Benign
0.16
Eigen_PC
Benign
0.15
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.64
T
MutationAssessor
Uncertain
2.4
M
PhyloP100
5.6
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.60
N
REVEL
Benign
0.16
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.67
T
Polyphen
0.82
P
Vest4
0.24
MutPred
0.28
Loss of MoRF binding (P = 0.0377);
MVP
0.49
MPC
0.22
ClinPred
0.54
D
GERP RS
4.1
Varity_R
0.17
gMVP
0.14
Mutation Taster
=89/11
polymorphism

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: rs786205161; hg19: chr21-44837559; API