6-32192157-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001276501.2(GPSM3):​c.136C>T​(p.Arg46Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

GPSM3
NM_001276501.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
Variant links:
Genes affected
GPSM3 (HGNC:13945): (G protein signaling modulator 3) Predicted to enable GTPase regulator activity. Predicted to be involved in positive regulation of inflammatory response. Predicted to act upstream of or within positive regulation of cytokine production involved in inflammatory response and positive regulation of leukocyte chemotaxis. Predicted to be located in cytoplasm and plasma membrane. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07067084).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPSM3NM_001276501.2 linkuse as main transcriptc.136C>T p.Arg46Cys missense_variant 2/4 ENST00000375040.8 NP_001263430.1
GPSM3NM_022107.3 linkuse as main transcriptc.136C>T p.Arg46Cys missense_variant 6/8 NP_071390.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPSM3ENST00000375040.8 linkuse as main transcriptc.136C>T p.Arg46Cys missense_variant 2/41 NM_001276501.2 ENSP00000364180 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.37e-7
AC:
1
AN:
1357294
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
663940
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:
9.43e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 06, 2023The c.136C>T (p.R46C) alteration is located in exon 6 (coding exon 2) of the GPSM3 gene. This alteration results from a C to T substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a cysteine (C). 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
0.090
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
23
DANN
Benign
0.66
DEOGEN2
Benign
0.025
T;T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.85
D;.;.
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
.;L;L
MutationTaster
Benign
0.89
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.75
N;N;N
REVEL
Benign
0.048
Sift
Benign
0.056
T;T;T
Sift4G
Benign
0.12
T;T;T
Polyphen
0.0
.;B;B
Vest4
0.32
MutPred
0.28
.;Loss of methylation at R46 (P = 0.0509);Loss of methylation at R46 (P = 0.0509);
MVP
0.068
MPC
0.60
ClinPred
0.22
T
GERP RS
1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.087
gMVP
0.28

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: rs1191563706; hg19: chr6-32159934; COSMIC: COSV66683701; COSMIC: COSV66683701; API