Variant chr12-47747550-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001098531.4(RAPGEF3):c.1550G>A(p.Cys517Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,613,702 control chromosomes in the GnomAD database, including 276 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 0.024 ( 137 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 139 hom. )

Consequence

RAPGEF3
NM_001098531.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

RAPGEF3 (HGNC:16629): (Rap guanine nucleotide exchange factor 3) Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including positive regulation of protein modification process; regulation of actin cytoskeleton organization; and regulation of syncytium formation by plasma membrane fusion. Located in filopodium; lamellipodium; and microvillus. Colocalizes with cortical actin cytoskeleton and plasma membrane. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

RAPGEF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002658397).

BP6

Variant 12-47747550-C-T is Benign according to our data. Variant chr12-47747550-C-T is described in ClinVar as [Benign]. Clinvar id is 786228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPGEF3	NM_001098531.4 linkuse as main transcript	c.1550G>A	p.Cys517Tyr	missense_variant	15/28	ENST00000449771.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPGEF3	ENST00000449771.7 linkuse as main transcript	c.1550G>A	p.Cys517Tyr	missense_variant	15/28	2	NM_001098531.4	P4	O95398-1

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3659

AN:

152208

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0838

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00637

AC:

1600

AN:

251018

Hom.:

AF XY:

0.00464

AC XY:

630

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0877

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00246

AC:

3600

AN:

1461376

Hom.:

139

Cov.:

AF XY:

0.00212

AC XY:

1540

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.0874

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.0240

AC:

3661

AN:

152326

Hom.:

137

Cov.:

AF XY:

0.0239

AC XY:

1780

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0836

Gnomad4 AMR

AF:

0.00882

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00426

Hom.:

Bravo

AF:

0.0265

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0801

AC:

353

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00775

AC:

941

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

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

Invitae

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.27

DEOGEN2

Benign

0.063

T;.;.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.032

MetaRNN

Benign

0.0027

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;N;.;N

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

1.2

N;N;N;N;N;N

REVEL

Benign

0.013

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;.;.;B;.;.

Vest4

0.10

MVP

0.47

MPC

0.33

ClinPred

0.00096

GERP RS

0.50

Varity_R

0.042

gMVP

0.27

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