Variant 3-15074864-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 156371.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBSN	NM_022340.4 linkuse as main transcript	c.1273G>A	p.Gly425Arg	missense_variant	14/14	ENST00000253699.7	NP_071735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBSN	ENST00000253699.7 linkuse as main transcript	c.1273G>A	p.Gly425Arg	missense_variant	14/14	1	NM_022340.4	ENSP00000253699	P1	Q9H1K0-1
RBSN	ENST00000476527.6 linkuse as main transcript	c.1273G>A	p.Gly425Arg	missense_variant	13/13	2		ENSP00000422551	P1	Q9H1K0-1
RBSN	ENST00000426541.1 linkuse as main transcript			downstream_gene_variant		3		ENSP00000403368

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

GnomAD3 exomes

AF:

0.00465

AC:

1160

AN:

249590

Hom.:

AF XY:

0.00519

AC XY:

701

AN XY:

135146

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 SAS exome

AF:

0.00715

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

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00759

Gnomad4 FIN exome

AF:

0.00736

Gnomad4 NFE exome

AF:

0.00575

Gnomad4 OTH exome

AF:

0.00475

GnomAD4 genome

AF:

0.00403

AC:

614

AN:

152384

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

335

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00703

Gnomad4 FIN

AF:

0.00771

Gnomad4 NFE

AF:

0.00597

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00467

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

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	RBSN: BS2 -
Uncertain significance, no assertion criteria provided	literature only	OMIM	Sep 20, 2014	- -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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

MutationTaster

Benign

1.0

D;D

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

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