Variant chr16-28905467-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024816.3(RABEP2):c.1538G>A(p.Arg513Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000547 in 1,609,336 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

RABEP2
NM_024816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

Variant links:

Genes affected

RABEP2 (HGNC:24817): (rabaptin, RAB GTPase binding effector protein 2) Predicted to enable GTPase activator activity and growth factor activity. Involved in regulation of cilium assembly. Located in cytosol; intracellular membrane-bounded organelle; and microtubule organizing center. [provided by Alliance of Genome Resources, Apr 2022]

RABEP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33687043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABEP2	NM_024816.3 linkuse as main transcript	c.1538G>A	p.Arg513Gln	missense_variant	12/13	ENST00000358201.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABEP2	ENST00000358201.9 linkuse as main transcript	c.1538G>A	p.Arg513Gln	missense_variant	12/13	1	NM_024816.3	P1	Q9H5N1-1
RABEP2	ENST00000357573.10 linkuse as main transcript	c.1430G>A	p.Arg477Gln	missense_variant	10/11	1			Q9H5N1-2
RABEP2	ENST00000544477.5 linkuse as main transcript	c.1325G>A	p.Arg442Gln	missense_variant	11/12	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000379

AC:

AN:

237532

Hom.:

AF XY:

0.0000465

AC XY:

AN XY:

129086

show subpopulations

Gnomad AFR exome

AF:

0.000417

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1457176

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

724392

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000290

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000324

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000474

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000248

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

Jun 22, 2024

The c.1538G>A (p.R513Q) alteration is located in exon 12 (coding exon 12) of the RABEP2 gene. This alteration results from a G to A substitution at nucleotide position 1538, causing the arginine (R) at amino acid position 513 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.6

.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.84

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.11

T;D;D

Sift4G

Benign

0.47

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.29

MVP

0.70

MPC

0.73

ClinPred

0.26

GERP RS

5.3

Varity_R

0.15

gMVP

0.088

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