Variant chr3-113019564-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015412.4(NEPRO):c.84G>A(p.Val28Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,613,754 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0027 ( 5 hom. )

Consequence

NEPRO
NM_015412.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.97

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-113019564-C-T is Benign according to our data. Variant chr3-113019564-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654036.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

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.84G>A	p.Val28Val	synonymous_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.84G>A	p.Val28Val	synonymous_variant	1/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00232

AC:

578

AN:

248980

Hom.:

AF XY:

0.00246

AC XY:

332

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00247

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00271

AC:

3959

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

1915

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00236

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00206

AC:

314

AN:

152388

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00322

Hom.:

Bravo

AF:

0.00190

EpiCase

AF:

0.00322

EpiControl

AF:

0.00373

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NEPRO-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

NEPRO: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.80

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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