chr17-5381483-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_004703.6(RABEP1):​c.2465T>G​(p.Val822Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RABEP1
NM_004703.6 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68
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]
NUP88 (HGNC:8067): (nucleoporin 88) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a mutagenesis_site Strongly decreases RAB5A binding affinity. (size 0) in uniprot entity RABE1_HUMAN
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.2465T>G p.Val822Gly missense_variant Exon 17 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.2465T>G p.Val822Gly missense_variant Exon 17 of 18 1 NM_004703.6 ENSP00000445408.2 Q15276-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2465T>G (p.V822G) alteration is located in exon 17 (coding exon 17) of the RABEP1 gene. This alteration results from a T to G substitution at nucleotide position 2465, causing the valine (V) at amino acid position 822 to be replaced by a glycine (G). 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
0.97
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.073
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-5.5
.;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0040
.;D
Sift4G
Uncertain
0.034
D;D
Polyphen
0.94
P;P
Vest4
0.66
MutPred
0.27
Loss of stability (P = 0.0011);.;
MVP
0.68
ClinPred
0.99
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.97
gMVP
0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-5284778; API