rs782178147
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPP5_Moderate
The NM_001099857.5(IKBKG):c.1167del(p.Glu390ArgfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 0)
Consequence
IKBKG
NM_001099857.5 frameshift
NM_001099857.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0810
Genes affected
IKBKG (HGNC:5961): (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma) This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 13 pathogenic variants in the truncated region.
PP5
?
Variant X-154564361-GC-G is Pathogenic according to our data. Variant chrX-154564361-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1220510.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154564361-GC-G is described in Lovd as [Pathogenic]. Variant chrX-154564361-GC-G is described in Lovd as [Pathogenic]. Variant chrX-154564361-GC-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IKBKG | NM_001099857.5 | c.1167del | p.Glu390ArgfsTer61 | frameshift_variant | 10/10 | ENST00000594239.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKBKG | ENST00000594239.6 | c.1167del | p.Glu390ArgfsTer61 | frameshift_variant | 10/10 | 1 | NM_001099857.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 0
GnomAD4 genome
?
Cov.:
0
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2020 | Published functional studies demonstrate that the c.1167delC variant completely abolishes IKBKG activity (Aradhya et al., 2001).; Frameshift variant predicted to result in protein extension, as the last 30 amino acids are replaced with 60 different amino acids, thus changing the properties of the 3-prime protein region; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 11179023, 24339369, 22121116) - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at