Genetic Variant SIKE1:p.Asp52His (chr1-114780454-C-G) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

SIKE1 links:

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
SIKE1	NM_025073.3 link	c.154G>C	p.Asp52His	missense_variant	Exon 1 of 5	ENST00000060969.6	NP_079349.2	Q9BRV8-1
SIKE1	NM_001102396.2 link	c.154G>C	p.Asp52His	missense_variant	Exon 1 of 5		NP_001095866.1	Q9BRV8-2
SIKE1	NR_049741.2 link	n.232G>C		non_coding_transcript_exon_variant	Exon 1 of 5
SIKE1	NR_049742.2 link	n.232G>C		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIKE1	ENST00000060969.6 link	c.154G>C	p.Asp52His	missense_variant	Exon 1 of 5	1	NM_025073.3	ENSP00000060969.6		Q9BRV8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249146

Hom.:

AF XY:

0.00000739

AC XY:

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:

AN:

1460614

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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.:

Alfa

AF:

0.0000935

Hom.:

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

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

0.052

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N

PrimateAI

Uncertain

0.50

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over