Variant 4-98352481-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001100427.2(RAP1GDS1):c.241A>G(p.Met81Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

RAP1GDS1
NM_001100427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32724088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GDS1	NM_001100427.2 linkuse as main transcript	c.241A>G	p.Met81Val	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.241A>G	p.Met81Val	missense_variant	4/15	2	NM_001100427.2	ENSP00000386153.4		P52306-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

249122

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135142

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:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461134

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726864

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:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

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

Mar 25, 2024

The c.244A>G (p.M82V) alteration is located in exon 4 (coding exon 4) of the RAP1GDS1 gene. This alteration results from a A to G substitution at nucleotide position 244, causing the methionine (M) at amino acid position 82 to be replaced by a valine (V). 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

0.29

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.023

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

Eigen

Benign

-0.079

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.015

MetaRNN

Benign

0.33

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

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

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.73

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

REVEL

Benign

0.15

Sift

Benign

0.47

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

Sift4G

Benign

0.46

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

Polyphen

0.019, 0.083

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

Vest4

0.80, 0.76, 0.72, 0.71, 0.81, 0.70

MutPred

0.53

.;.;.;.;Gain of ubiquitination at K77 (P = 0.078);.;Gain of ubiquitination at K77 (P = 0.078);.;

MVP

0.48

MPC

0.18

ClinPred

0.24

GERP RS

5.8

Varity_R

0.34

gMVP

0.55

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