Variant 3-113013348-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015412.4(NEPRO):c.397G>A(p.Glu133Lys) variant causes a missense change. The variant allele was found at a frequency of 0.01 in 1,613,834 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 9 hom., cov: 32)

Exomes 𝑓: 0.010 ( 85 hom. )

Consequence

NEPRO
NM_015412.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.43

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046730638).

BP6

Variant 3-113013348-C-T is Benign according to our data. Variant chr3-113013348-C-T is described in ClinVar as [Benign]. Clinvar id is 774846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEPRO	NM_015412.4 linkuse as main transcript	c.397G>A	p.Glu133Lys	missense_variant	4/9	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.397G>A	p.Glu133Lys	missense_variant	4/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.00859

AC:

1306

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00877

AC:

2205

AN:

251402

Hom.:

AF XY:

0.00899

AC XY:

1221

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00973

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00552

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.0102

AC:

14893

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

7311

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00546

Gnomad4 FIN exome

AF:

0.0211

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00857

AC:

1304

AN:

152194

Hom.:

Cov.:

AF XY:

0.00906

AC XY:

674

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.00982

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0262

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.00825

Hom.:

Bravo

AF:

0.00671

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.00844

AC:

1025

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0100

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	NEPRO: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 27, 2018	- -

NEPRO-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as likely 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.42

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0070

D;.

Polyphen

1.0

D;.

Vest4

0.87

MVP

0.81

MPC

0.63

ClinPred

0.037

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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