3-101852208-C-T

Position:

• chr3-101852208-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031419.4(NFKBIZ):​c.413C>T​(p.Ala138Val) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFKBIZ NM_031419.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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]

NFKBIZ (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055727333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIZ	NM_031419.4	c.413C>T	p.Ala138Val	missense_variant	2/12	ENST00000326172.9	NP_113607.1
NFKBIZ	NM_001005474.3	c.113C>T	p.Ala38Val	missense_variant	3/13		NP_001005474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIZ	ENST00000326172.9	c.413C>T	p.Ala138Val	missense_variant	2/12	1	NM_031419.4	ENSP00000325663.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.413C>T (p.A138V) alteration is located in exon 2 (coding exon 2) of the NFKBIZ gene. This alteration results from a C to T substitution at nucleotide position 413, causing the alanine (A) at amino acid position 138 to be replaced by a valine (V). 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	0.075
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	.;.;.;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.72	T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.056	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;L;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.78	N;N;N;N;D
REVEL	Benign	0.035
Sift	Benign	0.067	T;T;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.0010, 0.22	.;.;B;B;.
Vest4		0.10, 0.071, 0.053
MutPred		0.12		.;.;Loss of ubiquitination at K133 (P = 0.0795);Loss of ubiquitination at K133 (P = 0.0795);.;
MVP		0.27
MPC		0.23
ClinPred		0.12	T
GERP RS		3.7
Varity_R		0.090
gMVP		0.14

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: chr3-101571052;