16-48543172-C-T

Variant names:

• chr16-48543172-C-T
• NM_153029.4:c.2423G>A

Variant summary

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

The NM_153029.4(N4BP1):​c.2423G>A​(p.Ser808Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: N4BP1 NM_153029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50

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]

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=0.24965888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N4BP1	NM_153029.4	c.2423G>A	p.Ser808Asn	missense_variant	Exon 7 of 7	ENST00000262384.4	NP_694574.3
N4BP1	XM_011523482.2	c.2315G>A	p.Ser772Asn	missense_variant	Exon 6 of 6		XP_011521784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
N4BP1	ENST00000262384.4	c.2423G>A	p.Ser808Asn	missense_variant	Exon 7 of 7	1	NM_153029.4	ENSP00000262384.3
N4BP1	ENST00000565423.5	n.257G>A		non_coding_transcript_exon_variant	Exon 3 of 3	4
N4BP1	ENST00000569027.1	n.528G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2423G>A (p.S808N) alteration is located in exon 7 (coding exon 7) of the N4BP1 gene. This alteration results from a G to A substitution at nucleotide position 2423, causing the serine (S) at amino acid position 808 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.077
Sift	Uncertain	0.024	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.063
MutPred		0.18		Loss of glycosylation at S808 (P = 0.0109);
MVP		0.67
MPC		0.12
ClinPred		0.58	D
GERP RS		4.2
Varity_R		0.17

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: chr16-48577083;