19-11397318-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001035223.4(RGL3):ā€‹c.1940C>Gā€‹(p.Ala647Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

RGL3
NM_001035223.4 missense

Scores

5
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RGL3NM_001035223.4 linkuse as main transcriptc.1940C>G p.Ala647Gly missense_variant 18/19 ENST00000380456.8 NP_001030300.3 Q3MIN7A0A0A0MRX4
RGL3NM_001161616.3 linkuse as main transcriptc.1958C>G p.Ala653Gly missense_variant 18/19 NP_001155088.2 Q3MIN7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RGL3ENST00000380456.8 linkuse as main transcriptc.1940C>G p.Ala647Gly missense_variant 18/191 NM_001035223.4 ENSP00000369823.3 A0A0A0MRX4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458654
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725496
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsJan 23, 2024The c.1958C>G (p.A653G) alteration is located in exon 18 (coding exon 18) of the RGL3 gene. This alteration results from a C to G substitution at nucleotide position 1958, causing the alanine (A) at amino acid position 653 to be replaced by a glycine (G). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;.
M_CAP
Benign
0.018
T
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Benign
-0.95
T
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.010
D;D
Vest4
0.65
MutPred
0.72
Loss of stability (P = 0.0363);.;
MVP
0.49
MPC
0.10
ClinPred
0.99
D
GERP RS
4.7
gMVP
0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11507994; API