Variant 17-5282491-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The ENST00000537505.6(RABEP1):c.5C>A(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,114 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: 30)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

RABEP1
ENST00000537505.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.535

Variant links:

Genes affected

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RABEP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity RABE1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3905508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABEP1	NM_004703.6 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/18	1	NM_004703.6	ENSP00000445408	P1	Q15276-1
RABEP1	ENST00000341923.10 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/17	1		ENSP00000339569		Q15276-2
RABEP1	ENST00000575475.2 linkuse as main transcript	n.170C>A		non_coding_transcript_exon_variant	1/14	1
RABEP1	ENST00000575991.1 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/3	4		ENSP00000459550

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.70e-7

AC:

AN:

1149114

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

556706

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:

0.00000105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 27, 2022

The c.5C>A (p.A2E) alteration is located in exon 1 (coding exon 1) of the RABEP1 gene. This alteration results from a C to A substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a glutamic acid (E). 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

0.23

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0059

T;T;.

Eigen

Benign

-0.027

Eigen_PC

Benign

-0.0088

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.19

T;T;T

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

.;L;L

MutationTaster

Benign

0.98

D;D;D;D;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.69

.;N;N

REVEL

Benign

0.15

Sift

Pathogenic

0.0

.;D;T

Sift4G

Uncertain

0.026

.;D;D

Polyphen

0.37, 0.51

.;B;P

Vest4

0.24, 0.24

MutPred

0.12

Gain of solvent accessibility (P = 0.08);Gain of solvent accessibility (P = 0.08);Gain of solvent accessibility (P = 0.08);

MVP

0.34

ClinPred

0.77

GERP RS

2.4

Varity_R

0.16

gMVP

0.36

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