Variant 9-125203020-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005833.4(RABEPK):c.7C>A(p.Gln3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RABEPK
NM_005833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

RABEPK (HGNC:16896): (Rab9 effector protein with kelch motifs) Predicted to be involved in receptor-mediated endocytosis and vesicle docking involved in exocytosis. Predicted to be located in cytoplasmic vesicle; cytosol; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

RABEPK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08740276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABEPK	NM_005833.4 linkuse as main transcript	c.7C>A	p.Gln3Lys	missense_variant	2/8	ENST00000373538.8	NP_005824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABEPK	ENST00000373538.8 linkuse as main transcript	c.7C>A	p.Gln3Lys	missense_variant	2/8	1	NM_005833.4	ENSP00000362639	P1	Q7Z6M1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251486

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.7C>A (p.Q3K) alteration is located in exon 2 (coding exon 1) of the RABEPK gene. This alteration results from a C to A substitution at nucleotide position 7, causing the glutamine (Q) at amino acid position 3 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

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0062

T;.;T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.76

T;T;T;.;.

M_CAP

Benign

0.0069

MetaRNN

Benign

0.087

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.72

N;N;.;N;N

REVEL

Benign

0.022

Sift

Uncertain

0.029

D;D;.;D;D

Sift4G

Uncertain

0.044

D;D;D;D;D

Polyphen

0.044

B;B;B;B;B

Vest4

0.29

MutPred

0.43

Gain of methylation at Q3 (P = 0.0115);Gain of methylation at Q3 (P = 0.0115);Gain of methylation at Q3 (P = 0.0115);Gain of methylation at Q3 (P = 0.0115);Gain of methylation at Q3 (P = 0.0115);

MVP

0.39

MPC

0.041

ClinPred

0.29

GERP RS

2.1

Varity_R

0.082

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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