Variant chr17-5335289-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004703.6(RABEP1):c.473G>A(p.Arg158Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RABEP1
NM_004703.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.49

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6 link	c.473G>A	p.Arg158Lys	missense_variant	Exon 4 of 18	ENST00000537505.6	NP_004694.2	Q15276-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RABEP1	ENST00000537505.6 link	c.473G>A	p.Arg158Lys	missense_variant	Exon 4 of 18	1	NM_004703.6	ENSP00000445408.2	Q15276-1
RABEP1	ENST00000341923.10 link	c.473G>A	p.Arg158Lys	missense_variant	Exon 4 of 17	1		ENSP00000339569.6	Q15276-2
RABEP1	ENST00000575475.2 link	n.509G>A		non_coding_transcript_exon_variant	Exon 3 of 14	1
RABEP1	ENST00000570487.1 link	c.203G>A	p.Arg68Lys	missense_variant	Exon 2 of 3	2		ENSP00000482983.1	A0A087WZZ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249446

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135340

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473G>A (p.R158K) alteration is located in exon 4 (coding exon 4) of the RABEP1 gene. This alteration results from a G to A substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 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

0.17

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Uncertain

0.58

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.050

.;N

REVEL

Benign

0.27

Sift

Benign

0.32

.;T

Sift4G

Benign

0.67

T;T

Polyphen

1.0

D;D

Vest4

0.69

MutPred

0.54

Gain of ubiquitination at R158 (P = 0.0066);Gain of ubiquitination at R158 (P = 0.0066);

MVP

0.53

ClinPred

0.81

GERP RS

6.0

Varity_R

0.20

gMVP

0.39

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