NM_031419.4:c.1904T>G

Variant names:

• chr3-101857152-T-G
• rs1043339
• NM_031419.4:c.1904T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031419.4(NFKBIZ):​c.1904T>G​(p.Leu635Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 27)
• Consequence: NFKBIZ NM_031419.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• Publications: 3 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33740297).

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.1904T>G	p.Leu635Arg	missense	Exon 10 of 12	NP_113607.1	Q9BYH8-1
	NFKBIZ	NM_001005474.3		c.1604T>G	p.Leu535Arg	missense	Exon 11 of 13	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.1904T>G	p.Leu635Arg	missense	Exon 10 of 12	ENSP00000325663.5	Q9BYH8-1
	NFKBIZ	ENST00000394054.6	TSL:1	c.1604T>G	p.Leu535Arg	missense	Exon 11 of 13	ENSP00000377618.2	Q9BYH8-2
	NFKBIZ	ENST00000483180.5	TSL:5	c.1604T>G	p.Leu535Arg	missense	Exon 10 of 11	ENSP00000419800.1	C9JZ23

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.0062	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		3.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.23
Sift	Benign	0.049	D
Sift4G	Uncertain	0.028	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.66		Gain of phosphorylation at S637 (P = 0.121)
MVP		0.21
MPC		0.76
ClinPred		0.92	D
GERP RS		6.0
Varity_R		0.46
gMVP		0.51
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs1043339; hg19: chr3-101575996;