Variant 6-89411893-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021244.5(RRAGD):c.101G>T(p.Gly34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,546,744 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

RRAGD
NM_021244.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.589

Variant links:

Genes affected

RRAGD (HGNC:19903): (Ras related GTP binding D) RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.[supplied by OMIM, Apr 2004]

RRAGD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027935386).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRAGD	NM_021244.5 link	c.101G>T	p.Gly34Val	missense_variant	1/7	ENST00000369415.9	NP_067067.1	Q9NQL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRAGD	ENST00000369415.9 link	c.101G>T	p.Gly34Val	missense_variant	1/7	1	NM_021244.5	ENSP00000358423.4		Q9NQL2-1
RRAGD	ENST00000359203.3 link	c.-57G>T		5_prime_UTR_variant	1/6	2		ENSP00000352131.2		Q9NQL2-2

Frequencies

GnomAD3 genomes

AF:

0.000981

AC:

149

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000604

AC:

AN:

147240

Hom.:

AF XY:

0.000553

AC XY:

AN XY:

79558

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:

0.0000862

Gnomad FIN exome

AF:

0.00237

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000815

AC:

1137

AN:

1394678

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

562

AN XY:

688884

show subpopulations

Gnomad4 AFR exome

AF:

0.0000631

Gnomad4 AMR exome

AF:

0.000110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000277

Gnomad4 SAS exome

AF:

0.0000376

Gnomad4 FIN exome

AF:

0.00235

Gnomad4 NFE exome

AF:

0.000918

Gnomad4 OTH exome

AF:

0.000620

GnomAD4 genome

AF:

0.000980

AC:

149

AN:

152066

Hom.:

Cov.:

AF XY:

0.000875

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000603

AC:

ExAC

AF:

0.000535

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.101G>T (p.G34V) alteration is located in exon 1 (coding exon 1) of the RRAGD gene. This alteration results from a G to T substitution at nucleotide position 101, causing the glycine (G) at amino acid position 34 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

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-0.014

Eigen_PC

Benign

0.088

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

REVEL

Benign

0.077

Sift

Benign

0.10

Sift4G

Uncertain

0.023

Polyphen

0.85

Vest4

0.15

MVP

0.21

MPC

2.0

ClinPred

0.11

GERP RS

3.7

Varity_R

0.23

gMVP

0.25

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