Genetic Variant RGL3:p.Arg593Gly (chr19-11397567-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001035223.4(RGL3):c.1777C>G(p.Arg593Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R593W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGL3
NM_001035223.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.195

Publications

0 publications found

Variant links:

Genes affected

RGL3 (HGNC:30282): (ral guanine nucleotide dissociation stimulator like 3) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in positive regulation of GTPase activity and small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RGL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07737112).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001035223.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL3	NM_001035223.4	MANE Select	c.1777C>G	p.Arg593Gly	missense	Exon 17 of 19	NP_001030300.3	Q3MIN7-1
	RGL3	NM_001161616.3		c.1795C>G	p.Arg599Gly	missense	Exon 17 of 19	NP_001155088.2	Q3MIN7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGL3	ENST00000380456.8	TSL:1 MANE Select	c.1777C>G	p.Arg593Gly	missense	Exon 17 of 19	ENSP00000369823.3	Q3MIN7-1
RGL3	ENST00000393423.7	TSL:1	c.1795C>G	p.Arg599Gly	missense	Exon 17 of 19	ENSP00000377075.3	Q3MIN7-2
RGL3	ENST00000920283.1		c.1816C>G	p.Arg606Gly	missense	Exon 17 of 19	ENSP00000590342.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711476

African (AFR)

AF:

0.00

AC:

AN:

32828

American (AMR)

AF:

0.00

AC:

AN:

40316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25562

East Asian (EAS)

AF:

0.00

AC:

AN:

38588

South Asian (SAS)

AF:

0.00

AC:

AN:

83826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5428

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097960

Other (OTH)

AF:

0.00

AC:

AN:

59342

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.20

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.0094

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.32

M_CAP

Benign

0.017

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

PhyloP100

-0.20

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.26

REVEL

Benign

0.036

Sift

Benign

0.53

Sift4G

Benign

0.41

Vest4

0.14

MutPred

0.23

Loss of methylation at R593 (P = 0.032)

MVP

0.13

MPC

0.14

ClinPred

0.16

GERP RS

-5.2

gMVP

0.41

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over