Variant chr3-113019557-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015412.4(NEPRO):c.91C>T(p.Pro31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,613,318 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0043 ( 6 hom., cov: 34)

Exomes 𝑓: 0.00049 ( 4 hom. )

Consequence

NEPRO
NM_015412.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.726

Variant links:

Genes affected

NEPRO (HGNC:24496): (nucleolus and neural progenitor protein) Predicted to be involved in negative regulation of neuron differentiation and positive regulation of Notch signaling pathway. Predicted to be located in nucleolus. Predicted to be active in nucleus. Implicated in anauxetic dysplasia 3. [provided by Alliance of Genome Resources, Apr 2022]

NEPRO links:

NEPRO-AS1 (HGNC:):

NEPRO-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037612915).

BP6

Variant 3-113019557-G-A is Benign according to our data. Variant chr3-113019557-G-A is described in ClinVar as [Benign]. Clinvar id is 3037671.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000489 (715/1460952) while in subpopulation AFR AF= 0.0177 (593/33442). AF 95% confidence interval is 0.0166. There are 4 homozygotes in gnomad4_exome. There are 297 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEPRO	NM_015412.4 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/9	ENST00000314400.10	NP_056227.2	Q6NW34-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEPRO	ENST00000314400.10 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

647

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00112

AC:

279

AN:

248356

Hom.:

AF XY:

0.000719

AC XY:

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000489

AC:

715

AN:

1460952

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

297

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00426

AC:

649

AN:

152366

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

307

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000588

Hom.:

Bravo

AF:

0.00490

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NEPRO-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.023

Sift

Benign

0.11

T;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.068

B;P

Vest4

0.19

MVP

0.23

MPC

0.15

ClinPred

0.019

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.22

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

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