dbSNP rs1277614843: RABEP2:p.Glu445Lys (chr16-28906109-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024816.3(RABEP2):c.1333G>A(p.Glu445Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,442,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RABEP2
NM_024816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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]

RABEP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3 link	c.1333G>A	p.Glu445Lys	missense_variant	Exon 9 of 13	ENST00000358201.9	NP_079092.2	Q9H5N1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RABEP2	ENST00000358201.9 link	c.1333G>A	p.Glu445Lys	missense_variant	Exon 9 of 13	1	NM_024816.3	ENSP00000350934.4	Q9H5N1-1
RABEP2	ENST00000357573.10 link	c.1237G>A	p.Glu413Lys	missense_variant	Exon 8 of 11	1		ENSP00000350186.6	Q9H5N1-2
RABEP2	ENST00000544477.5 link	c.1120G>A	p.Glu374Lys	missense_variant	Exon 8 of 12	2		ENSP00000442798.1	B4DHR0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1442486

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33188

American (AMR)

AF:

0.0000242

AC:

AN:

41260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25682

East Asian (EAS)

AF:

0.00

AC:

AN:

38758

South Asian (SAS)

AF:

0.0000238

AC:

AN:

84058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104058

Other (OTH)

AF:

0.00

AC:

AN:

59654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

Dec 31, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1333G>A (p.E445K) alteration is located in exon 9 (coding exon 9) of the RABEP2 gene. This alteration results from a G to A substitution at nucleotide position 1333, causing the glutamic acid (E) at amino acid position 445 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

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.52

.;D;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.088

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.7

.;M;.

PhyloP100

4.0

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.059

T;D;T

Polyphen

1.0

D;D;D

Vest4

0.93

MVP

0.75

MPC

0.45

ClinPred

0.96

GERP RS

5.2

Varity_R

0.53

gMVP

0.76

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over