U.S. flag

An official website of the United States government

NM_001099857.5(IKBKG):c.-16+344G>C AND Immunodeficiency 33

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 18, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001172483.3

Allele description [Variation Report for NM_001099857.5(IKBKG):c.-16+344G>C]

NM_001099857.5(IKBKG):c.-16+344G>C

Gene:
IKBKG:inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001099857.5(IKBKG):c.-16+344G>C
HGVS:
  • NC_000023.11:g.154548089G>C
  • NG_009015.2:g.4484C>G
  • NG_009896.1:g.10846G>C
  • NM_001099856.6:c.190-3899G>C
  • NM_001099857.5:c.-16+344G>CMANE SELECT
  • NM_001145255.4:c.-16+344G>C
  • NM_001321396.3:c.-15-3899G>C
  • NM_001321397.3:c.-16+344G>C
  • NM_001377312.1:c.-15-3899G>C
  • NM_001377313.1:c.-15-3899G>C
  • NM_001377314.1:c.-16+344G>C
  • NM_001377315.1:c.-16+344G>C
  • NM_003639.4:c.-16G>C
  • LRG_70:g.10846G>C
  • NC_000023.10:g.153776304G>C
  • c.1-16G-C
Links:
OMIM: 300248.0030; dbSNP: rs2070806148
NCBI 1000 Genomes Browser:
rs2070806148
Molecular consequence:
  • NM_003639.4:c.-16G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001099856.6:c.190-3899G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001099857.5:c.-16+344G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001145255.4:c.-16+344G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001321396.3:c.-15-3899G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001321397.3:c.-16+344G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001377312.1:c.-15-3899G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001377313.1:c.-15-3899G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001377314.1:c.-16+344G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001377315.1:c.-16+344G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Immunodeficiency 33 (IMD33)
Synonyms:
Immunodeficiency without anhidrotic ectodermal dysplasia; X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency
Identifiers:
MONDO: MONDO:0010386; MedGen: C1970879; Orphanet: 319605; Orphanet: 319612; OMIM: 300636

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001335513OMIM
no assertion criteria provided
Pathogenic
(Jul 18, 2024) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

IKBKG (NEMO) 5' Untranslated Splice Mutations Lead to Severe, Chronic Disseminated Mycobacterial Infections.

Hsu AP, Zerbe CS, Foruraghi L, Iovine NM, Leiding JW, Mushatt DM, Wild L, Kuhns DB, Holland SM.

Clin Infect Dis. 2018 Jul 18;67(3):456-459. doi: 10.1093/cid/ciy186.

PubMed [citation]
PMID:
29534156
PMCID:
PMC6051446

Details of each submission

From OMIM, SCV001335513.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 3 adult males from 2 unrelated families (families A and B) with immunodeficiency-33 (IMD33; 300636) manifest as disseminated mycobacterial infections, Hsu et al. (2018) identified a hemizygous c.1-16G-C transversion at the last base of the first untranslated exon. Analysis of patient cells showed a splicing abnormality, resulting in a 110-bp deletion at the 3-prime end of exon 1. This molecular defect resulted in decreased transcript and protein levels compared to controls (about 30%). Cells derived from the patients in families A and B failed to upregulate cytokines in response to certain TLR agonists, suggesting that this IKBKG mutation is hypomorphic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 29, 2024