Genetic Variant N4BP1:p.Asp794Glu (chr16-48543213-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153029.4(N4BP1):c.2382C>A(p.Asp794Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,411,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

N4BP1
NM_153029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

N4BP1 (HGNC:29850): (NEDD4 binding protein 1) Enables mRNA binding activity; ribonuclease activity; and ubiquitin binding activity. Involved in cellular response to UV and negative regulation of viral genome replication. Predicted to be located in cytosol and nucleolus. Predicted to be active in PML body. [provided by Alliance of Genome Resources, Apr 2022]

N4BP1 links:

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ACMG classification

Classification made for transcript

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=0.08067772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N4BP1	NM_153029.4 link	c.2382C>A	p.Asp794Glu	missense_variant	Exon 7 of 7	ENST00000262384.4	NP_694574.3	O75113
N4BP1	XM_011523482.2 link	c.2274C>A	p.Asp758Glu	missense_variant	Exon 6 of 6		XP_011521784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
N4BP1	ENST00000262384.4 link	c.2382C>A	p.Asp794Glu	missense_variant	Exon 7 of 7	1	NM_153029.4	ENSP00000262384.3	O75113
N4BP1	ENST00000565423.5 link	n.216C>A		non_coding_transcript_exon_variant	Exon 3 of 3	4
N4BP1	ENST00000569027.1 link	n.487C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000954

AC:

AN:

209718

Hom.:

AF XY:

0.00000891

AC XY:

AN XY:

112226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000206

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1411162

Hom.:

Cov.:

AF XY:

0.00000575

AC XY:

AN XY:

695636

show subpopulations

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:

0.00000553

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2382C>A (p.D794E) alteration is located in exon 7 (coding exon 7) of the N4BP1 gene. This alteration results from a C to A substitution at nucleotide position 2382, causing the aspartic acid (D) at amino acid position 794 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.013

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.71

M_CAP

Benign

0.0058

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.14

REVEL

Benign

0.049

Sift

Benign

0.45

Sift4G

Benign

1.0

Polyphen

0.081

Vest4

0.070

MutPred

0.30

Gain of catalytic residue at D794 (P = 0.1545);

MVP

0.36

MPC

0.13

ClinPred

0.15

GERP RS

4.1

Varity_R

0.036

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over