16-28905420-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024816.3(RABEP2):​c.1585G>C​(p.Val529Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V529M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RABEP2
NM_024816.3 missense

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.24

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RABEP2NM_024816.3 linkc.1585G>C p.Val529Leu missense_variant Exon 12 of 13 ENST00000358201.9 NP_079092.2 Q9H5N1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RABEP2ENST00000358201.9 linkc.1585G>C p.Val529Leu missense_variant Exon 12 of 13 1 NM_024816.3 ENSP00000350934.4 Q9H5N1-1
RABEP2ENST00000357573.10 linkc.1477G>C p.Val493Leu missense_variant Exon 10 of 11 1 ENSP00000350186.6 Q9H5N1-2
RABEP2ENST00000544477.5 linkc.1372G>C p.Val458Leu missense_variant Exon 11 of 12 2 ENSP00000442798.1 B4DHR0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454462
Hom.:
0
Cov.:
32
AF XY:
0.00000277
AC XY:
2
AN XY:
722826
show subpopulations
African (AFR)
AF:
0.0000598
AC:
2
AN:
33440
American (AMR)
AF:
0.00
AC:
0
AN:
43630
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25772
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39476
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84356
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52258
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
9.01e-7
AC:
1
AN:
1109690
Other (OTH)
AF:
0.00
AC:
0
AN:
60144
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
.;D;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.085
D
MetaRNN
Pathogenic
0.77
D;D;D
MetaSVM
Uncertain
0.058
D
MutationAssessor
Uncertain
2.6
.;M;.
PhyloP100
5.2
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0020
D;D;D
Sift4G
Benign
0.31
T;T;T
Polyphen
1.0
D;D;D
Vest4
0.73
MutPred
0.18
.;Loss of MoRF binding (P = 0.0979);.;
MVP
0.80
MPC
0.60
ClinPred
0.94
D
GERP RS
5.3
Varity_R
0.32
gMVP
0.38
Mutation Taster
=60/40
polymorphism

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

Other links and lift over

dbSNP: rs774012300; hg19: chr16-28916741; API