3-15074864-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_022340.4(RBSN):c.1273G>A(p.Gly425Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,614,112 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 34 hom. )

Consequence

RBSN
NM_022340.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 7.56

Publications

12 publications found

Variant links:

Genes affected

RBSN (HGNC:20759): (rabenosyn, RAB effector) This gene encodes a protein that belongs to the FYVE zinc finger family of proteins. The encoded protein interacts with Ras-related proteins that regulate membrane trafficking. A missense mutation in this gene is associated with a defect in the early endocytic pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

RBSN Gene-Disease associations (from GenCC):

congenital neutropenia-myelofibrosis-nephromegaly syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RBSN links:

ENSG00000289750 (HGNC:):

ENSG00000289750 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075536966).

BP6

Variant 3-15074864-C-T is Benign according to our data. Variant chr3-15074864-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 156371.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBSN	NM_022340.4 link	c.1273G>A	p.Gly425Arg	missense_variant	Exon 14 of 14	ENST00000253699.7	NP_071735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBSN	ENST00000253699.7 link	c.1273G>A	p.Gly425Arg	missense_variant	Exon 14 of 14	1	NM_022340.4	ENSP00000253699.3

Frequencies

GnomAD3 genomes

AF:

0.00404

AC:

615

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00723

Gnomad FIN

AF:

0.00771

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00597

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00465

AC:

1160

AN:

249590

AF XY:

0.00519

show subpopulations

Gnomad AFR exome

AF:

0.000500

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00742

Gnomad NFE exome

AF:

0.00627

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00539

AC:

7879

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

4060

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33478

American (AMR)

AF:

0.00119

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00759

AC:

655

AN:

86250

European-Finnish (FIN)

AF:

0.00736

AC:

392

AN:

53294

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00575

AC:

6391

AN:

1111986

Other (OTH)

AF:

0.00475

AC:

287

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

525

1050

1574

2099

2624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00403

AC:

614

AN:

152384

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

335

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.000769

AC:

AN:

41594

American (AMR)

AF:

0.00307

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00703

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00771

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00597

AC:

406

AN:

68034

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.00309

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00543

AC:

659

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Sep 20, 2014

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RBSN: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.090

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

.;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

M;M

PhyloP100

7.6

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.20

Sift

Uncertain

0.028

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.98

D;D

Vest4

0.74

MutPred

0.32

Gain of methylation at G425 (P = 0.0183);Gain of methylation at G425 (P = 0.0183);

MVP

0.53

MPC

1.2

ClinPred

0.055

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.56

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over