1-192184489-C-G

Variant summary

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

The NM_130782.3(RGS18):​c.643C>G​(p.Arg215Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,459,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

RGS18
NM_130782.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.882
Variant links:
Genes affected
RGS18 (HGNC:14261): (regulator of G protein signaling 18) This gene encodes a member of the regulator of G-protein signaling family. This protein is contains a conserved, 120 amino acid motif called the RGS domain. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
ENSG00000285280 (HGNC:49018): (RSG2 antisense RNA 1)

Genome browser will be placed here

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=0.38427567).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGS18NM_130782.3 linkc.643C>G p.Arg215Gly missense_variant Exon 5 of 5 ENST00000367460.4 NP_570138.1 Q9NS28

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RGS18ENST00000367460.4 linkc.643C>G p.Arg215Gly missense_variant Exon 5 of 5 1 NM_130782.3 ENSP00000356430.3 Q9NS28
ENSG00000285280ENST00000643151.1 linkn.558G>C non_coding_transcript_exon_variant Exon 7 of 8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1459746
Hom.:
0
Cov.:
31
AF XY:
0.0000262
AC XY:
19
AN XY:
726258
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:
0.0000279
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.643C>G (p.R215G) alteration is located in exon 5 (coding exon 5) of the RGS18 gene. This alteration results from a C to G substitution at nucleotide position 643, causing the arginine (R) at amino acid position 215 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
Pathogenic
0.88
BayesDel_addAF
Benign
0.00086
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0080
D
Polyphen
1.0
D
Vest4
0.41
MutPred
0.49
Loss of stability (P = 0.0236);
MVP
0.83
MPC
0.32
ClinPred
0.96
D
GERP RS
4.7
Varity_R
0.38
gMVP
0.60

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.

Other links and lift over

dbSNP: rs868020301; hg19: chr1-192153619; API