Variant 13-32442975-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001320836.3(N4BP2L2):c.2849A>T(p.Asn950Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

N4BP2L2
NM_001320836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

Variant links:

Genes affected

N4BP2L2 (HGNC:26916): (NEDD4 binding protein 2 like 2) Enables enzyme binding activity. Involved in negative regulation of hematopoietic stem cell differentiation and positive regulation of hematopoietic stem cell proliferation. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

N4BP2L2 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=0.07550934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
N4BP2L2	NM_001320836.3 link	c.2849A>T	p.Asn950Ile	missense_variant	7/10	NP_001307765.1
N4BP2L2	NM_001387001.1 link	c.2849A>T	p.Asn950Ile	missense_variant	7/10	NP_001373930.1
N4BP2L2	NM_001387002.1 link	c.2849A>T	p.Asn950Ile	missense_variant	7/10	NP_001373931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
N4BP2L2	ENST00000380121.7 link	n.1533A>T		non_coding_transcript_exon_variant	5/8	1
N4BP2L2	ENST00000399396.7 link	c.1562A>T	p.Asn521Ile	missense_variant	7/10	5	ENSP00000382328.3	Q92802-3
N4BP2L2	ENST00000357505.10 link	c.1517A>T	p.Asn506Ile	missense_variant	7/10	2	ENSP00000350104.6	B4DPY1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000129

AC:

AN:

248856

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000580

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:

0.000239

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1461476

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000138

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000554

AC:

ESP6500EA

AF:

0.000491

AC:

ExAC

AF:

0.000149

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.1562A>T (p.N521I) alteration is located in exon 7 (coding exon 6) of the N4BP2L2 gene. This alteration results from a A to T substitution at nucleotide position 1562, causing the asparagine (N) at amino acid position 521 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.5

DANN

Benign

0.96

DEOGEN2

Benign

0.012

T;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.68

T;T;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.058

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.57

P;P;P

Vest4

0.24

MVP

0.23

MPC

0.052

ClinPred

0.059

GERP RS

-1.5

gMVP

0.064

Splicing

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