Variant chr3-113008337-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015412.4(NEPRO):c.1069T>A(p.Phe357Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,612,980 control chromosomes in the GnomAD database, including 434,956 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 31622 hom., cov: 32)

Exomes 𝑓: 0.73 ( 403334 hom. )

Consequence

NEPRO
NM_015412.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.281

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4119079E-6).

BP6

Variant 3-113008337-A-T is Benign according to our data. Variant chr3-113008337-A-T is described in ClinVar as [Benign]. Clinvar id is 1192595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEPRO	NM_015412.4 linkuse as main transcript	c.1069T>A	p.Phe357Ile	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.1069T>A	p.Phe357Ile	missense_variant	8/9	1	NM_015412.4	ENSP00000320251.5		Q6NW34-1

Frequencies

GnomAD3 genomes

AF:

0.608

AC:

92459

AN:

151984

Hom.:

31614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.731

Gnomad ASJ

AF:

0.800

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.776

Gnomad OTH

AF:

0.646

GnomAD3 exomes

AF:

0.679

AC:

170707

AN:

251324

Hom.:

61216

AF XY:

0.684

AC XY:

92936

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.793

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.770

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.735

AC:

1073209

AN:

1460878

Hom.:

403334

Cov.:

AF XY:

0.732

AC XY:

532320

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.767

Gnomad4 ASJ exome

AF:

0.788

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.616

Gnomad4 FIN exome

AF:

0.658

Gnomad4 NFE exome

AF:

0.774

Gnomad4 OTH exome

AF:

0.708

GnomAD4 genome

AF:

0.608

AC:

92482

AN:

152102

Hom.:

31622

Cov.:

AF XY:

0.603

AC XY:

44813

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.731

Gnomad4 ASJ

AF:

0.800

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.641

Gnomad4 NFE

AF:

0.776

Gnomad4 OTH

AF:

0.649

Alfa

AF:

0.742

Hom.:

32381

Bravo

AF:

0.598

TwinsUK

AF:

0.764

AC:

2834

ALSPAC

AF:

0.763

AC:

2940

ESP6500AA

AF:

0.298

AC:

1315

ESP6500EA

AF:

0.775

AC:

6663

ExAC

AF:

0.669

AC:

81271

Asia WGS

AF:

0.501

AC:

1742

AN:

3478

EpiCase

AF:

0.775

EpiControl

AF:

0.771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Anauxetic dysplasia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.5

DANN

Benign

0.90

DEOGEN2

Benign

0.0057

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.031

Sift

Benign

0.53

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0050

B;B

Vest4

0.18

MPC

0.19

ClinPred

0.0065

GERP RS

0.15

Varity_R

0.032

gMVP

0.27

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