3-101849914-C-T

Variant names:

• chr3-101849914-C-T
• NM_031419.4:c.286C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031419.4(NFKBIZ):​c.286C>T​(p.Pro96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,268,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: NFKBIZ NM_031419.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hereditary nonpolyposis colon cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ENSG00000297105 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12826416).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031419.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	NM_031419.4	MANE Select	c.286C>T	p.Pro96Ser	missense	Exon 1 of 12	NP_113607.1	Q9BYH8-1
	NFKBIZ	NM_001005474.3		c.-11-2171C>T		intron	N/A	NP_001005474.1	Q9BYH8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	ENST00000326172.9	TSL:1 MANE Select	c.286C>T	p.Pro96Ser	missense	Exon 1 of 12	ENSP00000325663.5	Q9BYH8-1
	NFKBIZ	ENST00000394054.6	TSL:1	c.-11-2171C>T		intron	N/A	ENSP00000377618.2	Q9BYH8-2
	NFKBIZ	ENST00000326151.9	TSL:2	c.286C>T	p.Pro96Ser	missense	Exon 1 of 13	ENSP00000325593.5	Q9BYH8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.88e-7 AC: 1 AN: 1268528 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 621592

African (AFR) AF: 0.00 AC: 0 AN: 25138

American (AMR) AF: 0.00 AC: 0 AN: 17416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19574

East Asian (EAS) AF: 0.00 AC: 0 AN: 28002

South Asian (SAS) AF: 0.00 AC: 0 AN: 63492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3678

European-Non Finnish (NFE) AF: 9.73e-7 AC: 1 AN: 1027798

Other (OTH) AF: 0.00 AC: 0 AN: 52676

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.057
Sift	Benign	0.19	T
Sift4G	Benign	0.53	T
Polyphen		0.013	B
Vest4		0.10
MutPred		0.17		Gain of phosphorylation at P96 (P = 0.0101)
MVP		0.15
MPC		0.24
ClinPred		0.27	T
GERP RS		2.3
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.066
gMVP		0.096
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr3-101568758;