3-101849775-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031419.4(NFKBIZ):​c.147C>G​(p.Asp49Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NFKBIZ
NM_031419.4 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.123
Variant links:
Genes affected
NFKBIZ (HGNC:29805): (NFKB inhibitor zeta) This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence similarity with the I kappa B family of proteins. The latter are known to play a role in inflammatory responses to LPS by their interaction with NF-B proteins through ankyrin-repeat domains. Studies in mouse indicate that this gene product is one of the nuclear I kappa B proteins and an activator of IL-6 production. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.099411696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFKBIZNM_031419.4 linkc.147C>G p.Asp49Glu missense_variant Exon 1 of 12 ENST00000326172.9 NP_113607.1 Q9BYH8-1
NFKBIZNM_001005474.3 linkc.-11-2310C>G intron_variant Intron 2 of 12 NP_001005474.1 Q9BYH8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NFKBIZENST00000326172.9 linkc.147C>G p.Asp49Glu missense_variant Exon 1 of 12 1 NM_031419.4 ENSP00000325663.5 Q9BYH8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.147C>G (p.D49E) alteration is located in exon 1 (coding exon 1) of the NFKBIZ gene. This alteration results from a C to G substitution at nucleotide position 147, causing the aspartic acid (D) at amino acid position 49 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
16
DANN
Benign
0.89
DEOGEN2
Benign
0.056
T;.;T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.38
T;T;T
M_CAP
Pathogenic
0.54
D
MetaRNN
Benign
0.099
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.71
.;N;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-2.4
N;N;N
REVEL
Benign
0.038
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.44
T;T;T
Polyphen
0.0020, 0.0090
.;B;B
Vest4
0.047, 0.063
MutPred
0.21
Gain of glycosylation at P45 (P = 0.1478);Gain of glycosylation at P45 (P = 0.1478);Gain of glycosylation at P45 (P = 0.1478);
MVP
0.19
MPC
0.23
ClinPred
0.082
T
GERP RS
1.9
Varity_R
0.052
gMVP
0.076

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-101568619; API