Variant 3-15073789-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022340.4(RBSN):c.2348C>G(p.Thr783Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000161 in 1,600,182 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: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RBSN
NM_022340.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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:

ENSG00000289750 (HGNC:):

ENSG00000289750 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07026595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBSN	NM_022340.4 linkuse as main transcript	c.2348C>G	p.Thr783Ser	missense_variant	14/14	ENST00000253699.7	NP_071735.2	Q9H1K0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBSN	ENST00000253699.7 linkuse as main transcript	c.2348C>G	p.Thr783Ser	missense_variant	14/14	1	NM_022340.4	ENSP00000253699.3	Q9H1K0-1
RBSN	ENST00000476527.6 linkuse as main transcript	c.2348C>G	p.Thr783Ser	missense_variant	13/13	2		ENSP00000422551.1	Q9H1K0-1
ENSG00000289750	ENST00000698784.1 linkuse as main transcript	n.1698+65C>G		intron_variant
ENSG00000289750	ENST00000698785.1 linkuse as main transcript	n.2894+65C>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000927

AC:

AN:

237318

Hom.:

AF XY:

0.0000861

AC XY:

AN XY:

127724

show subpopulations

Gnomad AFR exome

AF:

0.0000619

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:

0.000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

244

AN:

1448112

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

113

AN XY:

719358

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000393

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

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

Dec 08, 2023

The c.2348C>G (p.T783S) alteration is located in exon 14 (coding exon 11) of the RBSN gene. This alteration results from a C to G substitution at nucleotide position 2348, causing the threonine (T) at amino acid position 783 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.11

Sift

Benign

0.15

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0

B;B

Vest4

0.040

MutPred

0.14

Gain of catalytic residue at T783 (P = 0.0439);Gain of catalytic residue at T783 (P = 0.0439);

MVP

0.33

MPC

0.33

ClinPred

0.034

GERP RS

3.6

Varity_R

0.21

gMVP

0.0060

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