Variant rs179363868 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM5

The NM_001099857.5(IKBKG):c.524G>A(p.Arg175Gln) variant causes a missense change. 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. R175P) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000098 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.0000030 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

IKBKG
NM_001099857.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74

Variant links:

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 links:

IKBKG (HGNC:):

IKBKG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKG	NM_001099857.5 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	5/10	ENST00000594239.6	NP_001093327.1	Q9Y6K9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKBKG	ENST00000594239.6 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	5/10	1	NM_001099857.5	ENSP00000471166.1		Q9Y6K9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

101770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28546

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000430

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000301

AC:

AN:

997040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

305558

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:

0.00000379

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000982

AC:

AN:

101791

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28579

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000430

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;.;T;T;T;T;.;T;T

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

D;D;.;D;T;D;D;D;D

M_CAP

Pathogenic

0.65

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.1

.;.;M;.;.;.;.;.;M

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.94

N;.;.;N;.;.;.;.;.

REVEL

Uncertain

0.33

Sift

Benign

0.060

T;.;.;D;.;.;.;.;.

Sift4G

Benign

0.10

T;T;T;T;T;T;T;D;T

Polyphen

1.0, 1.0

.;D;D;.;.;.;.;.;D

Vest4

0.23, 0.22, 0.23, 0.21, 0.22

MutPred

0.17

Loss of MoRF binding (P = 0.0113);.;Loss of MoRF binding (P = 0.0113);.;Loss of MoRF binding (P = 0.0113);.;.;.;Loss of MoRF binding (P = 0.0113);

MVP

0.97

ClinPred

0.77

GERP RS

4.1

Varity_R

0.12

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over