Variant 3-113008375-G-T 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.1031C>A(p.Ser344Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,613,186 control chromosomes in the GnomAD database, including 357 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 0.015 ( 45 hom., cov: 32)

Exomes 𝑓: 0.017 ( 312 hom. )

Consequence

NEPRO
NM_015412.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.33

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029225051).

BP6

Variant 3-113008375-G-T is Benign according to our data. Variant chr3-113008375-G-T is described in ClinVar as [Benign]. Clinvar id is 3056605.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2236/152290) while in subpopulation NFE AF= 0.0161 (1095/68020). AF 95% confidence interval is 0.0153. There are 45 homozygotes in gnomad4. There are 1245 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEPRO	NM_015412.4 linkuse as main transcript	c.1031C>A	p.Ser344Tyr	missense_variant	8/9	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.1031C>A	p.Ser344Tyr	missense_variant	8/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2237

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0711

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0157

AC:

3942

AN:

250924

Hom.:

AF XY:

0.0158

AC XY:

2146

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.00888

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00425

Gnomad FIN exome

AF:

0.0674

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0167

AC:

24328

AN:

1460896

Hom.:

312

Cov.:

AF XY:

0.0163

AC XY:

11833

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.00897

Gnomad4 ASJ exome

AF:

0.00804

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00400

Gnomad4 FIN exome

AF:

0.0646

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0147

AC:

2236

AN:

152290

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1245

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0711

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0107

TwinsUK

AF:

0.0186

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0160

AC:

138

ExAC

AF:

0.0150

AC:

1820

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0143

EpiControl

AF:

0.0161

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

Apr 24, 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

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

0.071

Eigen_PC

Benign

0.075

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.0

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.097

Sift

Benign

0.044

D;T

Sift4G

Benign

0.11

T;T

Polyphen

0.046

B;B

Vest4

0.12

MPC

0.20

ClinPred

0.043

GERP RS

5.5

Varity_R

0.12

gMVP

0.18

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