rs1242981163

Variant names:

• chr19-35896421-C-A
• ENST00000606253.5:c.832G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-35896421-C-A
• chr19-35896421-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032721.3(NFKBID):​c.832G>T​(p.Ala278Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NFKBID NM_032721.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBID	NM_032721.3	c.832G>T	p.Ala278Ser	missense_variant	Exon 7 of 12		NP_116110.2
NFKBID	NM_139239.5	c.802G>T	p.Ala268Ser	missense_variant	Exon 7 of 12		NP_640332.2
NFKBID	NM_001365706.3	c.802G>T	p.Ala268Ser	missense_variant	Exon 7 of 10		NP_001352635.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBID	ENST00000641389.3	c.802G>T	p.Ala268Ser	missense_variant	Exon 7 of 12			ENSP00000493265.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	.;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D;T;T;T
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	.;L;.;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.3	.;N;.;.
REVEL	Uncertain	0.44
Sift	Benign	0.065	.;T;.;.
Sift4G	Uncertain	0.015	.;D;.;.
Polyphen		1.0, 1.0	.;D;D;.
Vest4		0.56
MutPred		0.69		.;Gain of glycosylation at A126 (P = 0.0279);.;.;
MVP		0.61
MPC		1.7
ClinPred		0.90	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15

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: chr19-36387323; COSMIC: COSV61729940; COSMIC: COSV61729940;