Variant 3-113011087-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015412.4(NEPRO):c.871G>A(p.Val291Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,610,442 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

NEPRO
NM_015412.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0400

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 (HGNC:):

NEPRO links:

GTPBP8 (HGNC:25007): (GTP binding protein 8 (putative)) Predicted to enable GTP binding activity and metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GTPBP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012369007).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEPRO	NM_015412.4 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant	6/9	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.871G>A	p.Val291Met	missense_variant	6/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.000953

AC:

145

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000930

AC:

231

AN:

248360

Hom.:

AF XY:

0.00103

AC XY:

138

AN XY:

134604

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.000735

Gnomad ASJ exome

AF:

0.000704

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00128

AC:

1862

AN:

1458152

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

916

AN XY:

725386

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.000887

Gnomad4 ASJ exome

AF:

0.000885

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000935

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00147

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.000952

AC:

145

AN:

152290

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00109

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000857

AC:

104

EpiCase

AF:

0.00104

EpiControl

AF:

0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NEPRO-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 27, 2023

The NEPRO c.871G>A variant is predicted to result in the amino acid substitution p.Val291Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-112729934-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.7

DANN

Benign

0.87

DEOGEN2

Benign

0.0079

T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.051

Sift

Benign

0.068

T;T

Sift4G

Benign

0.067

T;T

Polyphen

0.14

B;P

Vest4

0.14

MVP

0.17

MPC

0.21

ClinPred

0.0056

GERP RS

3.7

Varity_R

0.035

gMVP

0.14

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