Variant 19-5924882-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007322.3(RANBP3):c.941C>T(p.Ala314Val) variant causes a missense change. The variant allele was found at a frequency of 0.00396 in 1,614,092 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts 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 0.020 ( 109 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 89 hom. )

Consequence

RANBP3
NM_007322.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

RANBP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018642545).

BP6

Variant 19-5924882-G-A is Benign according to our data. Variant chr19-5924882-G-A is described in ClinVar as [Benign]. Clinvar id is 773081.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP3	NM_007322.3 linkuse as main transcript	c.941C>T	p.Ala314Val	missense_variant	11/17	ENST00000340578.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP3	ENST00000340578.10 linkuse as main transcript	c.941C>T	p.Ala314Val	missense_variant	11/17	1	NM_007322.3	P3	Q9H6Z4-1

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3044

AN:

152204

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0685

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00543

AC:

1354

AN:

249584

Hom.:

AF XY:

0.00393

AC XY:

532

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0705

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000609

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00228

AC:

3339

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1458

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0678

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000328

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.0200

AC:

3054

AN:

152322

Hom.:

109

Cov.:

AF XY:

0.0195

AC XY:

1453

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0686

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00490

Hom.:

Bravo

AF:

0.0225

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0613

AC:

249

ESP6500EA

AF:

0.000835

AC:

ExAC

AF:

0.00646

AC:

782

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.0

N;N;.;N;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.0050

D;D;.;T;.;.

Sift4G

Benign

0.45

T;T;T;T;T;D

Polyphen

0.57

P;B;P;P;.;.

Vest4

0.30

MVP

0.46

MPC

0.54

ClinPred

0.016

GERP RS

5.3

Varity_R

0.072

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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