Variant chr13-32407334-T-G 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_052818.3(N4BP2L1):c.312A>C(p.Arg104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

N4BP2L1
NM_052818.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302

Variant links:

Genes affected

N4BP2L1 (HGNC:25037): (NEDD4 binding protein 2 like 1)

N4BP2L1 links:

Genome browser will be placed here

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=0.19627073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N4BP2L1	NM_052818.3 link	c.312A>C	p.Arg104Ser	missense_variant	3/5	ENST00000380130.7	NP_438169.2	Q5TBK1-1A0A024RDR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
N4BP2L1	ENST00000380130.7 link	c.312A>C	p.Arg104Ser	missense_variant	3/5	1	NM_052818.3	ENSP00000369473.2		Q5TBK1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251408

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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 06, 2021

The c.312A>C (p.R104S) alteration is located in exon 3 (coding exon 3) of the N4BP2L1 gene. This alteration results from a A to C substitution at nucleotide position 312, causing the arginine (R) at amino acid position 104 to be replaced by a serine (S). 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

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.088

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.85

.;T;T;.

M_CAP

Benign

0.0075

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;L;L;L

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.4

D;.;D;D

REVEL

Benign

0.26

Sift

Benign

0.070

T;.;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.11

B;B;D;D

Vest4

0.56

MutPred

0.53

Loss of MoRF binding (P = 0.0241);Loss of MoRF binding (P = 0.0241);Loss of MoRF binding (P = 0.0241);Loss of MoRF binding (P = 0.0241);

MVP

0.24

MPC

0.64

ClinPred

0.22

GERP RS

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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