chr3-101853377-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_031419.4(NFKBIZ):c.851C>T(p.Ala284Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,614,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 1 hom. )
Consequence
NFKBIZ
NM_031419.4 missense
NM_031419.4 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 3.17
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.02108121).
BS2
?
High AC in GnomAd at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKBIZ | NM_031419.4 | c.851C>T | p.Ala284Val | missense_variant | 5/12 | ENST00000326172.9 | |
NFKBIZ | NM_001005474.3 | c.551C>T | p.Ala184Val | missense_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKBIZ | ENST00000326172.9 | c.851C>T | p.Ala284Val | missense_variant | 5/12 | 1 | NM_031419.4 | P4 | |
NFKBIZ | ENST00000394054.6 | c.551C>T | p.Ala184Val | missense_variant | 6/13 | 1 | A2 | ||
NFKBIZ | ENST00000483180.5 | c.551C>T | p.Ala184Val | missense_variant | 5/11 | 5 | |||
NFKBIZ | ENST00000326151.9 | c.708+143C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000211 AC: 53AN: 251462Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135904
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GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461892Hom.: 1 Cov.: 33 AF XY: 0.000121 AC XY: 88AN XY: 727246
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GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74452
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | The c.851C>T (p.A284V) alteration is located in exon 5 (coding exon 5) of the NFKBIZ gene. This alteration results from a C to T substitution at nucleotide position 851, causing the alanine (A) at amino acid position 284 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.049
.;.;B
Vest4
0.13, 0.10
MVP
MPC
0.27
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at