Variant 9-133102048-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000372050.8(RALGDS):c.2101G>A(p.Gly701Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,560,734 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

RALGDS
ENST00000372050.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

Variant links:

Genes affected

RALGDS (HGNC:9842): (ral guanine nucleotide dissociation stimulator) Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes.[supplied by OMIM, Nov 2010]

RALGDS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 162 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGDS	NM_006266.4 linkuse as main transcript	c.2101G>A	p.Gly701Arg	missense_variant	15/18	ENST00000372050.8	NP_006257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGDS	ENST00000372050.8 linkuse as main transcript	c.2101G>A	p.Gly701Arg	missense_variant	15/18	1	NM_006266.4	ENSP00000361120	A2	Q12967-1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000545

AC:

AN:

168728

Hom.:

AF XY:

0.000581

AC XY:

AN XY:

89532

show subpopulations

Gnomad AFR exome

AF:

0.000102

Gnomad AMR exome

AF:

0.00334

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000426

Gnomad FIN exome

AF:

0.0000629

Gnomad NFE exome

AF:

0.0000294

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.000133

AC:

188

AN:

1408430

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

100

AN XY:

695646

show subpopulations

Gnomad4 AFR exome

AF:

0.000124

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000646

Gnomad4 OTH exome

AF:

0.0000342

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152304

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000257

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

Aug 10, 2021

The c.2101G>A (p.G701R) alteration is located in exon 15 (coding exon 15) of the RALGDS gene. This alteration results from a G to A substitution at nucleotide position 2101, causing the glycine (G) at amino acid position 701 to be replaced by an arginine (R). 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

0.32

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

D;.;.;.;.;T;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

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

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.014

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

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.4

M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.012

D;D;D;D;D;D;.

Sift4G

Benign

0.17

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

Polyphen

1.0

D;.;.;.;.;.;.

Vest4

0.68

MutPred

0.31

.;.;.;.;.;.;Gain of solvent accessibility (P = 6e-04);

MVP

0.79

MPC

0.38

ClinPred

0.10

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: 1

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