ENST00000606253.5:c.1235A>C

Variant names:

• chr19-35889999-T-G
• ENST00000606253.5:c.1235A>C

Variant summary

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

The ENST00000606253.5(NFKBID):​c.1235A>C​(p.Gln412Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFKBID ENST00000606253.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

Genes affected

NFKBID (HGNC:15671): (NFKB inhibitor delta) Predicted to enable NF-kappaB binding activity. Predicted to be involved in T cell receptor signaling pathway; positive regulation of T-helper 17 cell differentiation; and regulation of gene expression. Predicted to act upstream of or within several processes, including negative regulation of NF-kappaB transcription factor activity; negative regulation of T cell differentiation in thymus; and positive regulation of thymocyte apoptotic process. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBID	NM_032721.3	c.1235A>C	p.Gln412Pro	missense_variant	Exon 11 of 12		NP_116110.2
NFKBID	NM_139239.5	c.1205A>C	p.Gln402Pro	missense_variant	Exon 11 of 12		NP_640332.2
NFKBID	NM_001321831.2	c.824A>C	p.Gln275Pro	missense_variant	Exon 11 of 12		NP_001308760.1
NFKBID	NM_001365705.1	c.779A>C	p.Gln260Pro	missense_variant	Exon 11 of 12		NP_001352634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBID	ENST00000641389.3	c.1205A>C	p.Gln402Pro	missense_variant	Exon 11 of 12			ENSP00000493265.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.779A>C (p.Q260P) alteration is located in exon 11 (coding exon 8) of the NFKBID gene. This alteration results from a A to C substitution at nucleotide position 779, causing the glutamine (Q) at amino acid position 260 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	0.23
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	.;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.027	.;D;.
Sift4G	Uncertain	0.050	.;T;.
Polyphen		1.0, 1.0	.;D;D
Vest4		0.51
MutPred		0.59		.;Gain of glycosylation at Q260 (P = 0.0316);.;
MVP		0.57
MPC		1.9
ClinPred		0.96	D
GERP RS		3.8
Varity_R		0.75

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: chr19-36380901;