Variant 19-5923893-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007322.3(RANBP3):c.1018G>A(p.Val340Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RANBP3
NM_007322.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0230

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:

RANBP3 (HGNC:):

RANBP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040717214).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP3	NM_007322.3 linkuse as main transcript	c.1018G>A	p.Val340Ile	missense_variant	12/17	ENST00000340578.10	NP_015561.1	Q9H6Z4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANBP3	ENST00000340578.10 linkuse as main transcript	c.1018G>A	p.Val340Ile	missense_variant	12/17	1	NM_007322.3	ENSP00000341483.5		Q9H6Z4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249308

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.1018G>A (p.V340I) alteration is located in exon 12 (coding exon 12) of the RANBP3 gene. This alteration results from a G to A substitution at nucleotide position 1018, causing the valine (V) at amino acid position 340 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.3

DANN

Uncertain

0.97

DEOGEN2

Benign

0.040

.;T;T;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.77

T;T;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.041

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.060

N;N;.;N;.

REVEL

Benign

0.035

Sift

Benign

0.14

T;T;.;T;.

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.33

B;B;B;B;.

Vest4

0.11

MutPred

0.13

.;Loss of loop (P = 0.0603);.;.;.;

MVP

0.26

MPC

0.39

ClinPred

0.041

GERP RS

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.11

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