6-31557735-T-A

Variant names:

• chr6-31557735-T-A
• NM_005007.4:c.442T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005007.4(NFKBIL1):​c.442T>A​(p.Trp148Arg) 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. 13/19 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: 32)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.641

Genes affected

NFKBIL1 (HGNC:7800): (NFKB inhibitor like 1) This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

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=0.083173096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.442T>A	p.Trp148Arg	missense_variant	Exon 3 of 4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.442T>A	p.Trp148Arg	missense_variant	Exon 3 of 4		NP_001138433.1
NFKBIL1	NM_001144962.2	c.373T>A	p.Trp125Arg	missense_variant	Exon 3 of 4		NP_001138434.1
NFKBIL1	NM_001144963.2	c.373T>A	p.Trp125Arg	missense_variant	Exon 3 of 4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.442T>A	p.Trp148Arg	missense_variant	Exon 3 of 4	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.442T>A (p.W148R) alteration is located in exon 3 (coding exon 3) of the NFKBIL1 gene. This alteration results from a T to A substitution at nucleotide position 442, causing the tryptophan (W) at amino acid position 148 to be replaced by an arginine (R). 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	0.33
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0077	T;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.49	T;.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.22	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.85	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.30
MutPred		0.35		.;Gain of disorder (P = 0.0267);Gain of disorder (P = 0.0267);
MVP		0.44
MPC		1.1
ClinPred		0.16	T
GERP RS		1.9
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr6-31525512;