1-114780454-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025073.3(SIKE1):​c.154G>C​(p.Asp52His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SIKE1
NM_025073.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24
Variant links:
Genes affected
SIKE1 (HGNC:26119): (suppressor of IKBKE 1) SIKE interacts with IKK-epsilon (IKBKE; MIM 605048) and TBK1 (MIM 604834) and acts as a suppressor of TLR3 (MIM 603029) and virus-triggered interferon activation pathways (Huang et al., 2005 [PubMed 16281057]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19442308).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIKE1NM_025073.3 linkc.154G>C p.Asp52His missense_variant Exon 1 of 5 ENST00000060969.6 NP_079349.2 Q9BRV8-1
SIKE1NM_001102396.2 linkc.154G>C p.Asp52His missense_variant Exon 1 of 5 NP_001095866.1 Q9BRV8-2
SIKE1NR_049741.2 linkn.232G>C non_coding_transcript_exon_variant Exon 1 of 5
SIKE1NR_049742.2 linkn.232G>C non_coding_transcript_exon_variant Exon 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIKE1ENST00000060969.6 linkc.154G>C p.Asp52His missense_variant Exon 1 of 5 1 NM_025073.3 ENSP00000060969.6 Q9BRV8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
249146
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135236
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460614
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726600
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000935
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.154G>C (p.D52H) alteration is located in exon 1 (coding exon 1) of the SIKE1 gene. This alteration results from a G to C substitution at nucleotide position 154, causing the aspartic acid (D) at amino acid position 52 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.019
.;T
Eigen
Benign
0.052
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.52
T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.39
N;N
REVEL
Benign
0.20
Sift
Benign
0.073
T;T
Sift4G
Benign
0.095
T;T
Polyphen
0.0010
B;B
Vest4
0.34
MutPred
0.39
Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP
0.65
MPC
0.43
ClinPred
0.57
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1170220485; hg19: chr1-115323075; API