rs179363865

Variant names:

• chrX-154563613-G-C
• rs179363865
• NM_001099857.5:c.967G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001099857.5(IKBKG):​c.967G>C​(p.Ala323Pro) variant causes a missense change. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: IKBKG NM_001099857.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 5.12
• Publications: 9 publications found

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]

IKBKG Gene-Disease associations (from GenCC):

• ectodermal dysplasia and immunodeficiency 1

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• IKBKG-related immunodeficiency with or without ectodermal dysplasia

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• incontinentia pigmenti

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, ClinGen, Orphanet
• ectodermal dysplasia and immune deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency 33

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099857.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKG	NM_001099857.5	MANE Select	c.967G>C	p.Ala323Pro	missense	Exon 8 of 10	NP_001093327.1	Q9Y6K9-1
	IKBKG	NM_001099856.6		c.1171G>C	p.Ala391Pro	missense	Exon 8 of 10	NP_001093326.2	Q9Y6K9-2
	IKBKG	NM_001321396.3		c.967G>C	p.Ala323Pro	missense	Exon 8 of 10	NP_001308325.1	Q9Y6K9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKG	ENST00000594239.6	TSL:1 MANE Select	c.967G>C	p.Ala323Pro	missense	Exon 8 of 10	ENSP00000471166.1	Q9Y6K9-1
	IKBKG	ENST00000618670.4	TSL:1	c.1171G>C	p.Ala391Pro	missense	Exon 8 of 10	ENSP00000483825.1	Q9Y6K9-2
	IKBKG	ENST00000611071.4	TSL:1	c.967G>C	p.Ala323Pro	missense	Exon 8 of 10	ENSP00000479662.1	Q9Y6K9-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.1
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.34
MutPred		0.18		Gain of glycosylation at A323 (P = 0.0105)
MVP		0.99
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.69
gMVP		0.73

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

Other links and lift over

dbSNP: rs179363865; hg19: chrX-153791828;