Variant rs179363895 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PS1_ModerateBP4

The NM_001099857.5(IKBKG):c.367C>T(p.Arg123Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 0 hem., cov: 12)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

IKBKG
NM_001099857.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.100

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 1 ACMG points.

PS1

Transcript NM_001099857.5 (IKBKG) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

BP4

Computational evidence support a benign effect (MetaRNN=0.2924406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKG	NM_001099857.5 linkuse as main transcript	c.367C>T	p.Arg123Trp	missense_variant	3/10	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.367C>T	p.Arg123Trp	missense_variant	3/10	1	NM_001099857.5	ENSP00000471166.1		Q9Y6K9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

77659

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11057

FAILED QC

Gnomad AFR

AF:

0.0000488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00101

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

338386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

117792

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000258

AC:

AN:

77659

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11057

show subpopulations

Gnomad4 AFR

AF:

0.0000488

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00101

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

UniProtKB/Swiss-Prot

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

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

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.87

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

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.29

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

MetaSVM

Uncertain

0.18

MutationAssessor

Benign

0.34

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

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.1

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

REVEL

Uncertain

0.51

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.0070

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0, 0.95, 0.88

.;.;D;.;P;.;.;.;.;P;P;.

Vest4

0.14, 0.13, 0.12, 0.079, 0.080, 0.11, 0.13

MutPred

0.36

Loss of MoRF binding (P = 0.0477);Loss of MoRF binding (P = 0.0477);.;Loss of MoRF binding (P = 0.0477);Loss of MoRF binding (P = 0.0477);.;Loss of MoRF binding (P = 0.0477);Loss of MoRF binding (P = 0.0477);Loss of MoRF binding (P = 0.0477);Loss of MoRF binding (P = 0.0477);Loss of MoRF binding (P = 0.0477);.;

MVP

0.96

ClinPred

0.65

GERP RS

1.4

Varity_R

0.11

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over