Genetic Variant NM_052818.3:c.92G>A (chr13-32427991-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052818.3(N4BP2L1):c.92G>A(p.Arg31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,556,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

N4BP2L1
NM_052818.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Publications

1 publications found

Variant links:

Genes affected

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

N4BP2L1 links:

ENSG00000270008 (HGNC:):

ENSG00000270008 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18159464).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
N4BP2L1	NM_052818.3	MANE Select	c.92G>A	p.Arg31Gln	missense	Exon 1 of 5	NP_438169.2	Q5TBK1-1
N4BP2L1	NM_001353627.2		c.92G>A	p.Arg31Gln	missense	Exon 1 of 7	NP_001340556.1
N4BP2L1	NM_001353628.2		c.92G>A	p.Arg31Gln	missense	Exon 1 of 7	NP_001340557.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
N4BP2L1	ENST00000380130.7	TSL:1 MANE Select	c.92G>A	p.Arg31Gln	missense	Exon 1 of 5	ENSP00000369473.2	Q5TBK1-1
N4BP2L1	ENST00000380133.6	TSL:1	c.92G>A	p.Arg31Gln	missense	Exon 1 of 6	ENSP00000369476.2	Q5TBK1-1
N4BP2L1	ENST00000380139.8	TSL:1	c.92G>A	p.Arg31Gln	missense	Exon 1 of 5	ENSP00000369484.3	Q5TBK1-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1404368

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29708

American (AMR)

AF:

0.00

AC:

AN:

34838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24196

East Asian (EAS)

AF:

0.00

AC:

AN:

34046

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

9.21e-7

AC:

AN:

1085798

Other (OTH)

AF:

0.00

AC:

AN:

57766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0086

Eigen

Benign

-0.050

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

1.4

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.070

REVEL

Benign

0.054

Sift

Benign

0.21

Sift4G

Benign

0.15

Polyphen

0.77

Vest4

0.37

MutPred

0.27

Gain of catalytic residue at P28 (P = 0)

MVP

0.043

MPC

1.1

ClinPred

0.53

GERP RS

3.7

PromoterAI

-0.054

Neutral

(source)

Varity_R

0.067

gMVP

0.30

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over