Variant 20-48629539-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_020820.4(PREX1):c.4676G>C(p.Ser1559Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,614,048 control chromosomes in the GnomAD database, including 8,054 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.085 ( 624 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7430 hom. )

Consequence

PREX1
NM_020820.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

PREX1 (HGNC:32594): (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins. [provided by RefSeq, Jul 2008]

PREX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, PREX1

BP4

Computational evidence support a benign effect (MetaRNN=0.0016014576).

BP6

Variant 20-48629539-C-G is Benign according to our data. Variant chr20-48629539-C-G is described in ClinVar as [Benign]. Clinvar id is 1296867.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PREX1	NM_020820.4 linkuse as main transcript	c.4676G>C	p.Ser1559Thr	missense_variant	37/40	ENST00000371941.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PREX1	ENST00000371941.4 linkuse as main transcript	c.4676G>C	p.Ser1559Thr	missense_variant	37/40	1	NM_020820.4	P1	Q8TCU6-1
PREX1	ENST00000482556.5 linkuse as main transcript	c.*94G>C		3_prime_UTR_variant, NMD_transcript_variant	19/22	2

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12926

AN:

152174

Hom.:

625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.0505

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0895

Gnomad OTH

AF:

0.0947

GnomAD3 exomes

AF:

0.105

AC:

26453

AN:

251270

Hom.:

1607

AF XY:

0.108

AC XY:

14601

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0475

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.0682

Gnomad NFE exome

AF:

0.0915

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0953

AC:

139324

AN:

1461756

Hom.:

7430

Cov.:

AF XY:

0.0970

AC XY:

70571

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.0726

Gnomad4 NFE exome

AF:

0.0883

Gnomad4 OTH exome

AF:

0.0999

GnomAD4 genome

AF:

0.0849

AC:

12937

AN:

152292

Hom.:

624

Cov.:

AF XY:

0.0860

AC XY:

6407

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0473

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0895

Gnomad4 OTH

AF:

0.0933

Alfa

AF:

0.0950

Hom.:

574

Bravo

AF:

0.0869

TwinsUK

AF:

0.0833

AC:

309

ALSPAC

AF:

0.0924

AC:

356

ESP6500AA

AF:

0.0504

AC:

222

ESP6500EA

AF:

0.0943

AC:

811

ExAC

AF:

0.103

AC:

12524

Asia WGS

AF:

0.125

AC:

434

AN:

3478

EpiCase

AF:

0.0940

EpiControl

AF:

0.0959

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.028

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.76

REVEL

Benign

0.030

Sift

Benign

0.20

Sift4G

Benign

0.36

Polyphen

0.35

Vest4

0.066

MPC

0.34

ClinPred

0.0064

GERP RS

1.8

Varity_R

0.047

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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