19-35888588-G-C

Variant names:

• chr19-35888588-G-C
• rs754675713
• NM_139239.5:c.1339C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139239.5(NFKBID):​c.1339C>G​(p.Arg447Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R447C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NFKBID NM_139239.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23999184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139239.5. 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
	NFKBID	NM_139239.5	MANE Select	c.1339C>G	p.Arg447Gly	missense	Exon 12 of 12	NP_640332.2	A0A286YF31
	NFKBID	NM_032721.3		c.1369C>G	p.Arg457Gly	missense	Exon 12 of 12	NP_116110.2
	NFKBID	NM_001321831.2		c.958C>G	p.Arg320Gly	missense	Exon 12 of 12	NP_001308760.1	A0AAQ5BIF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBID	ENST00000641389.3	MANE Select	c.1339C>G	p.Arg447Gly	missense	Exon 12 of 12	ENSP00000493265.2	A0A286YF31
	NFKBID	ENST00000606253.5	TSL:1	c.1369C>G	p.Arg457Gly	missense	Exon 12 of 12	ENSP00000475712.2	Q8NI38-2
	NFKBID	ENST00000590828.5	TSL:1	n.*420C>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000467127.1	K7ENW9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.15
Sift	Benign	0.055	T
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.32		Loss of MoRF binding (P = 5e-04)
MVP		0.48
MPC		0.97
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.17
Mutation Taster		=68/32	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: rs754675713; hg19: chr19-36379490;