9-113507324-A-G
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000374136.5(RGS3):āc.1A>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,680 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 (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
RGS3
ENST00000374136.5 start_lost
ENST00000374136.5 start_lost
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 2.45
Genes affected
RGS3 (HGNC:9999): (regulator of G protein signaling 3) This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. Long isoforms are largely cytosolic and plasma membrane-associated with a function in Wnt signaling and in the epithelial mesenchymal transition, while shorter N-terminally-truncated isoforms can be nuclear. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RGS3 | NM_001394167.1 | c.787A>G | p.Met263Val | missense_variant | 11/23 | ENST00000695401.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RGS3 | ENST00000695401.1 | c.787A>G | p.Met263Val | missense_variant | 11/23 | NM_001394167.1 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250004Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135280
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461486Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727016
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74356
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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 | Nov 03, 2023 | The c.1123A>G (p.M375V) alteration is located in exon 14 (coding exon 13) of the RGS3 gene. This alteration results from a A to G substitution at nucleotide position 1123, causing the methionine (M) at amino acid position 375 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.;.
MutationTaster
Benign
D;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;B;B;B;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at