Variant 3-15074132-C-T 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.2005G>A(p.Glu669Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000012 ( 0 hom. )

Consequence

RBSN
NM_022340.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

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=0.21300018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBSN	NM_022340.4 linkuse as main transcript	c.2005G>A	p.Glu669Lys	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.2005G>A	p.Glu669Lys	missense_variant	14/14	1	NM_022340.4	ENSP00000253699.3	Q9H1K0-1
RBSN	ENST00000476527.6 linkuse as main transcript	c.2005G>A	p.Glu669Lys	missense_variant	13/13	2		ENSP00000422551.1	Q9H1K0-1
ENSG00000289750	ENST00000698784.1 linkuse as main transcript	n.1420G>A		non_coding_transcript_exon_variant	8/9
ENSG00000289750	ENST00000698785.1 linkuse as main transcript	n.2616G>A		non_coding_transcript_exon_variant	14/17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251128

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135686

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727238

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

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

Apr 07, 2023

The c.2005G>A (p.E669K) alteration is located in exon 14 (coding exon 11) of the RBSN gene. This alteration results from a G to A substitution at nucleotide position 2005, causing the glutamic acid (E) at amino acid position 669 to be replaced by a lysine (K). 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

0.085

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

T;T

Eigen

Benign

0.089

Eigen_PC

Benign

0.060

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

.;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.18

Sift

Benign

0.12

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.92

P;P

Vest4

0.28

MVP

0.50

MPC

0.54

ClinPred

0.35

GERP RS

5.5

Varity_R

0.15

gMVP

0.12

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