Variant 16-28910938-T-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_024816.3(RABEP2):c.1039A>T(p.Thr347Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,612,940 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 1 hom. )

Consequence

RABEP2
NM_024816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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:

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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=0.06801233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABEP2	NM_024816.3 linkuse as main transcript	c.1039A>T	p.Thr347Ser	missense_variant	7/13	ENST00000358201.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABEP2	ENST00000358201.9 linkuse as main transcript	c.1039A>T	p.Thr347Ser	missense_variant	7/13	1	NM_024816.3	P1	Q9H5N1-1
RABEP2	ENST00000357573.10 linkuse as main transcript	c.943A>T	p.Thr315Ser	missense_variant	6/11	1			Q9H5N1-2
RABEP2	ENST00000562590.5 linkuse as main transcript	n.1560A>T		non_coding_transcript_exon_variant	7/7	1
RABEP2	ENST00000544477.5 linkuse as main transcript	c.826A>T	p.Thr276Ser	missense_variant	6/12	2

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

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:

0.00100

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000490

AC:

121

AN:

246808

Hom.:

AF XY:

0.000544

AC XY:

AN XY:

134132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000557

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.000908

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000972

AC:

1420

AN:

1460798

Hom.:

Cov.:

AF XY:

0.000961

AC XY:

698

AN XY:

726600

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000488

Gnomad4 FIN exome

AF:

0.0000943

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000519

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000241

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:

0.00100

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000502

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00108

AC:

ExAC

AF:

0.000496

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.00107

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

Sep 15, 2021

The c.1039A>T (p.T347S) alteration is located in exon 7 (coding exon 7) of the RABEP2 gene. This alteration results from a A to T substitution at nucleotide position 1039, causing the threonine (T) at amino acid position 347 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.062

.;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

.;N;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.050

N;N;N

REVEL

Benign

0.059

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.11

B;B;B

Vest4

0.31

MutPred

0.38

.;Gain of phosphorylation at T347 (P = 0.088);.;

MVP

0.51

MPC

0.17

ClinPred

0.035

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.055

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

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