chr1-114776441-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025073.3(SIKE1):​c.427G>A​(p.Asp143Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D143H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SIKE1
NM_025073.3 missense

Scores

3
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIKE1NM_025073.3 linkc.427G>A p.Asp143Asn missense_variant Exon 4 of 5 ENST00000060969.6 NP_079349.2 Q9BRV8-1
SIKE1NM_001102396.2 linkc.439G>A p.Asp147Asn missense_variant Exon 4 of 5 NP_001095866.1 Q9BRV8-2
SIKE1NR_049741.2 linkn.567G>A non_coding_transcript_exon_variant Exon 4 of 5
SIKE1NR_049742.2 linkn.399G>A non_coding_transcript_exon_variant Exon 3 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIKE1ENST00000060969.6 linkc.427G>A p.Asp143Asn missense_variant Exon 4 of 5 1 NM_025073.3 ENSP00000060969.6 Q9BRV8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251250
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135830
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458496
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725792
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
.;T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.028
D;D
Polyphen
0.99
D;D
Vest4
0.39
MutPred
0.59
.;Loss of disorder (P = 0.0857);
MVP
0.86
MPC
1.1
ClinPred
0.99
D
GERP RS
6.2
Varity_R
0.43
gMVP
0.26

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: rs141025380; hg19: chr1-115319062; API