Variant 4-98352553-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001100427.2(RAP1GDS1):c.313G>A(p.Val105Met) variant causes a missense change. The variant allele was found at a frequency of 0.00439 in 1,614,048 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 31 hom. )

Consequence

RAP1GDS1
NM_001100427.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

RAP1GDS1 (HGNC:9859): (Rap1 GTPase-GDP dissociation stimulator 1) The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]

RAP1GDS1 links:

RAP1GDS1 (HGNC:):

RAP1GDS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009418279).

BP6

Variant 4-98352553-G-A is Benign according to our data. Variant chr4-98352553-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654961.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GDS1	NM_001100427.2 linkuse as main transcript	c.313G>A	p.Val105Met	missense_variant	4/15	ENST00000408927.8	NP_001093897.1	P52306-1B3KNU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1GDS1	ENST00000408927.8 linkuse as main transcript	c.313G>A	p.Val105Met	missense_variant	4/15	2	NM_001100427.2	ENSP00000386153.4		P52306-1

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

577

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00389

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00467

AC:

1164

AN:

249494

Hom.:

AF XY:

0.00443

AC XY:

599

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.00565

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.00466

Gnomad OTH exome

AF:

0.00594

GnomAD4 exome

AF:

0.00446

AC:

6513

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

3104

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00593

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.00450

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.00379

AC:

577

AN:

152304

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00405

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000525

AC:

ESP6500EA

AF:

0.00351

AC:

ExAC

AF:

0.00443

AC:

536

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

RAP1GDS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;.;.;T;.;.;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0094

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.49

.;.;.;.;N;.;N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.17

T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.012

D;T;T;D;T;T;T;T

Polyphen

0.84, 0.77

.;.;.;.;P;.;P;.

Vest4

0.69, 0.70, 0.67, 0.67, 0.69, 0.66

MVP

0.63

MPC

0.25

ClinPred

0.022

GERP RS

5.8

Varity_R

0.20

gMVP

0.51

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