6-32191828-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001276501.2(GPSM3):​c.226C>T​(p.Arg76Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GPSM3
NM_001276501.2 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPSM3NM_001276501.2 linkuse as main transcriptc.226C>T p.Arg76Cys missense_variant 3/4 ENST00000375040.8 NP_001263430.1
GPSM3NM_022107.3 linkuse as main transcriptc.226C>T p.Arg76Cys missense_variant 7/8 NP_071390.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPSM3ENST00000375040.8 linkuse as main transcriptc.226C>T p.Arg76Cys missense_variant 3/41 NM_001276501.2 ENSP00000364180 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152016
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000815
AC:
2
AN:
245262
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134052
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000909
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460336
Hom.:
0
Cov.:
32
AF XY:
0.00000551
AC XY:
4
AN XY:
726518
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152016
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
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 GeneticsDec 17, 2023The c.226C>T (p.R76C) alteration is located in exon 7 (coding exon 3) of the GPSM3 gene. This alteration results from a C to T substitution at nucleotide position 226, causing the arginine (R) at amino acid position 76 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
Pathogenic
0.81
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.50
D;D;D
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.22
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.91
D;.;.
M_CAP
Benign
0.0065
T
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.0
.;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-8.0
D;D;D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.58
MutPred
0.64
.;Gain of catalytic residue at L77 (P = 0.0267);Gain of catalytic residue at L77 (P = 0.0267);
MVP
0.16
MPC
1.4
ClinPred
1.0
D
GERP RS
3.2
Varity_R
0.16
gMVP
0.67

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: rs1195543020; hg19: chr6-32159605; API