6-31558043-A-C

Position:

• chr6-31558043-A-C

Variant summary

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

The NM_005007.4(NFKBIL1):​c.578A>C​(p.Gln193Pro) 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. 14/19 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.791

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=0.085264206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.578A>C	p.Gln193Pro	missense_variant	4/4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.533A>C	p.Gln178Pro	missense_variant	4/4		NP_001138433.1
NFKBIL1	NM_001144962.2	c.509A>C	p.Gln170Pro	missense_variant	4/4		NP_001138434.1
NFKBIL1	NM_001144963.2	c.464A>C	p.Gln155Pro	missense_variant	4/4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.578A>C	p.Gln193Pro	missense_variant	4/4	1	NM_005007.4	ENSP00000365318.4
NFKBIL1	ENST00000376145.8	c.533A>C	p.Gln178Pro	missense_variant	4/4	1		ENSP00000365315.4
NFKBIL1	ENST00000376146.8	c.509A>C	p.Gln170Pro	missense_variant	4/4	4		ENSP00000365316.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1253004 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 621204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Nov 13, 2024

The c.578A>C (p.Q193P) alteration is located in exon 4 (coding exon 4) of the NFKBIL1 gene. This alteration results from a A to C substitution at nucleotide position 578, causing the glutamine (Q) at amino acid position 193 to be replaced by a proline (P). 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	0.060
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.0019	T;.;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.22	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.38	T;T;T
Sift4G	Benign	0.31	T;T;D
Polyphen		0.0	B;.;.
Vest4		0.16
MutPred		0.36		.;Gain of helix (P = 0.0034);.;
MVP		0.22
MPC		0.75
ClinPred		0.056	T
GERP RS		0.36
gMVP		0.24

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: chr6-31525820;