rs764364995

Variant summary

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

The NM_004703.6(RABEP1):​c.49C>T​(p.Arg17Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,608,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RABEP1
NM_004703.6 missense

Scores

8
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
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]

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
RABEP1NM_004703.6 linkc.49C>T p.Arg17Trp missense_variant Exon 2 of 18 ENST00000537505.6 NP_004694.2 Q15276-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RABEP1ENST00000537505.6 linkc.49C>T p.Arg17Trp missense_variant Exon 2 of 18 1 NM_004703.6 ENSP00000445408.2 Q15276-1
RABEP1ENST00000341923.10 linkc.49C>T p.Arg17Trp missense_variant Exon 2 of 17 1 ENSP00000339569.6 Q15276-2
RABEP1ENST00000575475.2 linkn.200-23241C>T intron_variant Intron 1 of 13 1
RABEP1ENST00000575991.1 linkc.235C>T p.Arg79Trp missense_variant Exon 3 of 3 4 ENSP00000459550.1 I3L2B8

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152054
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000123
AC:
3
AN:
244838
Hom.:
0
AF XY:
0.00000754
AC XY:
1
AN XY:
132688
show subpopulations
Gnomad AFR exome
AF:
0.000130
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:
0.00000894
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1456362
Hom.:
0
Cov.:
30
AF XY:
0.00000414
AC XY:
3
AN XY:
724168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152054
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000166
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.49C>T (p.R17W) alteration is located in exon 2 (coding exon 2) of the RABEP1 gene. This alteration results from a C to T substitution at nucleotide position 49, causing the arginine (R) at amino acid position 17 to be replaced by a tryptophan (W). 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
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Benign
-0.42
T
MutationAssessor
Uncertain
2.5
.;M;M
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-1.6
.;.;N
REVEL
Benign
0.20
Sift
Uncertain
0.0020
.;.;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.75, 0.76
MutPred
0.37
.;Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);
MVP
0.64
ClinPred
0.85
D
GERP RS
5.6
Varity_R
0.28
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs764364995; hg19: chr17-5212003; API