Genetic Variant NM_024816.3:c.1039A>T (chr16-28910938-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 15/22 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

Publications

3 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06801233).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024816.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP2	NM_024816.3	MANE Select	c.1039A>T	p.Thr347Ser	missense	Exon 7 of 13	NP_079092.2	Q9H5N1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RABEP2	ENST00000358201.9	TSL:1 MANE Select	c.1039A>T	p.Thr347Ser	missense	Exon 7 of 13	ENSP00000350934.4	Q9H5N1-1
RABEP2	ENST00000357573.10	TSL:1	c.943A>T	p.Thr315Ser	missense	Exon 6 of 11	ENSP00000350186.6	Q9H5N1-2
RABEP2	ENST00000562590.5	TSL:1	n.1560A>T		non_coding_transcript_exon	Exon 7 of 7

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

GnomAD2 exomes

AF:

0.000490

AC:

121

AN:

246808

AF XY:

0.000544

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 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

African (AFR)

AF:

0.0000896

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000488

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

53014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00120

AC:

1331

AN:

1111568

Other (OTH)

AF:

0.000646

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

159

238

318

397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

156

208

260

<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

AF:

0.000519

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.062

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.73

M_CAP

Benign

0.0070

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PhyloP100

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.050

REVEL

Benign

0.059

Sift

Benign

0.42

Sift4G

Benign

0.79

Polyphen

0.11

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

Mutation Taster

=93/7

polymorphism

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over