3-101852948-C-T

Variant summary

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

The NM_031419.4(NFKBIZ):​c.523C>T​(p.Pro175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. P175T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NFKBIZ
NM_031419.4 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36
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=0.09949526).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFKBIZNM_031419.4 linkc.523C>T p.Pro175Ser missense_variant Exon 4 of 12 ENST00000326172.9 NP_113607.1 Q9BYH8-1
NFKBIZNM_001005474.3 linkc.223C>T p.Pro75Ser missense_variant Exon 5 of 13 NP_001005474.1 Q9BYH8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NFKBIZENST00000326172.9 linkc.523C>T p.Pro175Ser missense_variant Exon 4 of 12 1 NM_031419.4 ENSP00000325663.5 Q9BYH8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.083
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
13
DANN
Benign
0.95
DEOGEN2
Benign
0.33
.;.;.;T;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.51
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.78
T;T;T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.099
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.2
.;.;L;L;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-2.1
N;N;D;N;D
REVEL
Benign
0.079
Sift
Benign
0.031
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
0.0030, 0.15
.;.;B;B;.
Vest4
0.22, 0.21, 0.18
MutPred
0.16
.;.;Gain of phosphorylation at P175 (P = 0.0417);Gain of phosphorylation at P175 (P = 0.0417);.;
MVP
0.17
MPC
0.26
ClinPred
0.12
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.058
gMVP
0.32

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: chr3-101571792; API