Variant 13-32443989-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001320836.3(N4BP2L2):c.1835C>T(p.Pro612Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,607,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

N4BP2L2
NM_001320836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0614264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
N4BP2L2	NM_001320836.3 link	c.1835C>T	p.Pro612Leu	missense_variant	7/10	NP_001307765.1
N4BP2L2	NM_001387001.1 link	c.1835C>T	p.Pro612Leu	missense_variant	7/10	NP_001373930.1
N4BP2L2	NM_001387002.1 link	c.1835C>T	p.Pro612Leu	missense_variant	7/10	NP_001373931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
N4BP2L2	ENST00000380121.7 link	n.519C>T		non_coding_transcript_exon_variant	5/8	1
N4BP2L2	ENST00000674422.1 link	c.1835C>T	p.Pro612Leu	missense_variant	8/8		ENSP00000501390.1	A0A6I8PU16
N4BP2L2	ENST00000399396.7 link	c.548C>T	p.Pro183Leu	missense_variant	7/10	5	ENSP00000382328.3	Q92802-3

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

240238

Hom.:

AF XY:

0.0000922

AC XY:

AN XY:

130136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000780

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:

0.0000370

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.0000598

AC:

AN:

1455318

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

723182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000819

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:

0.0000388

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000987

AC:

AN:

151930

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000745

AC:

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

Jul 20, 2021

The c.548C>T (p.P183L) alteration is located in exon 7 (coding exon 6) of the N4BP2L2 gene. This alteration results from a C to T substitution at nucleotide position 548, causing the proline (P) at amino acid position 183 to be replaced by a leucine (L). 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

-0.39

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.017

T;.;T;T

Eigen

Benign

-0.0037

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.66

T;T;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-0.76

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.20

T;T;T;.

Sift4G

Benign

0.14

T;T;T;T

Polyphen

1.0

D;D;D;.

Vest4

0.12

MVP

0.74

MPC

0.055

ClinPred

0.064

GERP RS

4.7

gMVP

0.048

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