Variant chr3-113011069-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015412.4(NEPRO):c.889G>A(p.Val297Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,601,718 control chromosomes in the GnomAD database, including 52 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 42 hom. )

Consequence

NEPRO
NM_015412.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00406757).

BP6

Variant 3-113011069-C-T is Benign according to our data. Variant chr3-113011069-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1176781.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEPRO	NM_015412.4 linkuse as main transcript	c.889G>A	p.Val297Ile	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.889G>A	p.Val297Ile	missense_variant	6/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00442

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00923

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00394

AC:

951

AN:

241160

Hom.:

AF XY:

0.00400

AC XY:

523

AN XY:

130874

show subpopulations

Gnomad AFR exome

AF:

0.000702

Gnomad AMR exome

AF:

0.000718

Gnomad ASJ exome

AF:

0.00234

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000209

Gnomad FIN exome

AF:

0.00438

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00541

AC:

7835

AN:

1449388

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

3805

AN XY:

720814

show subpopulations

Gnomad4 AFR exome

AF:

0.000557

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00227

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000203

Gnomad4 FIN exome

AF:

0.00460

Gnomad4 NFE exome

AF:

0.00651

Gnomad4 OTH exome

AF:

0.00367

GnomAD4 genome

AF:

0.00508

AC:

774

AN:

152330

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00442

Gnomad4 NFE

AF:

0.00923

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00726

Hom.:

Bravo

AF:

0.00415

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00710

AC:

ExAC

AF:

0.00391

AC:

474

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

NEPRO: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.015

Sift

Benign

0.083

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.12

B;B

Vest4

0.15

MVP

0.21

MPC

0.15

ClinPred

0.0077

GERP RS

1.7

Varity_R

0.019

gMVP

0.16

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