21-43417080-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_173354.5(SIK1):​c.2014G>A​(p.Gly672Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G672R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Failed GnomAD Quality Control

Consequence

SIK1
NM_173354.5 missense

Scores

1
18

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0310
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.043696582).
BP6
Variant 21-43417080-C-T is Benign according to our data. Variant chr21-43417080-C-T is described in ClinVar as [Benign]. Clinvar id is 476096.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIK1NM_173354.5 linkc.2014G>A p.Gly672Ser missense_variant Exon 14 of 14 ENST00000270162.8 NP_775490.2 P57059
SIK1XM_011529474.3 linkc.1867G>A p.Gly623Ser missense_variant Exon 13 of 13 XP_011527776.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIK1ENST00000270162.8 linkc.2014G>A p.Gly672Ser missense_variant Exon 14 of 14 1 NM_173354.5 ENSP00000270162.6 P57059

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
9366
Hom.:
0
Cov.:
0
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000123
AC:
1
AN:
81624
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
45758
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000806
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
9380
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
4338
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000931
AC:
1

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 30 Benign:1
Jul 30, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.81
DANN
Benign
0.71
DEOGEN2
Benign
0.073
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
-1.3
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.13
N
REVEL
Benign
0.11
Sift
Benign
0.53
T
Sift4G
Benign
0.95
T
Polyphen
0.0
B
Vest4
0.052
MutPred
0.15
Gain of glycosylation at G672 (P = 0.0045);
MVP
0.30
MPC
0.14
ClinPred
0.030
T
GERP RS
-6.0
Varity_R
0.022
gMVP
0.059

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751934560; hg19: chr21-44836960; API