Variant 4-98391976-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100427.2(RAP1GDS1):c.533A>G(p.Asn178Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,609,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

RAP1GDS1
NM_001100427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06363034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1GDS1	NM_001100427.2 linkuse as main transcript	c.533A>G	p.Asn178Ser	missense_variant	6/15	ENST00000408927.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1GDS1	ENST00000408927.8 linkuse as main transcript	c.533A>G	p.Asn178Ser	missense_variant	6/15	2	NM_001100427.2	A1	P52306-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000772

AC:

AN:

246124

Hom.:

AF XY:

0.0000899

AC XY:

AN XY:

133540

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000170

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

317

AN:

1457126

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

177

AN XY:

724874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000132

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000489

AC:

ExAC

AF:

0.0000745

AC:

EpiCase

AF:

0.000329

EpiControl

AF:

0.000179

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

Oct 27, 2022

The c.536A>G (p.N179S) alteration is located in exon 6 (coding exon 6) of the RAP1GDS1 gene. This alteration results from a A to G substitution at nucleotide position 536, causing the asparagine (N) at amino acid position 179 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

0.056

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.018

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

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.020

MetaRNN

Benign

0.064

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.60

D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.70

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

REVEL

Benign

0.069

Sift

Benign

0.85

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

Sift4G

Benign

0.45

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

Polyphen

0.0, 0.0030

.;.;.;B;.;.;.;B;.

Vest4

0.17, 0.11, 0.10, 0.18, 0.097

MVP

0.068

MPC

0.13

ClinPred

0.054

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.074

gMVP

0.16

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