chr9-136338575-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001145638.3(GPSM1):c.839G>A(p.Arg280Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00009 in 1,611,142 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R280W) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000095 ( 1 hom. )
Consequence
GPSM1
NM_001145638.3 missense
NM_001145638.3 missense
Scores
2
8
4
Clinical Significance
Conservation
PhyloP100: 6.61
Genes affected
GPSM1 (HGNC:17858): (G protein signaling modulator 1) G-protein signaling modulators (GPSMs) play diverse functional roles through their interaction with G-protein subunits. This gene encodes a receptor-independent activator of G protein signaling, which is one of several factors that influence the basal activity of G-protein signaling systems. The protein contains seven tetratricopeptide repeats in its N-terminal half and four G-protein regulatory (GPR) motifs in its C-terminal half. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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 | UniProt |
---|---|---|---|---|---|---|---|
GPSM1 | NM_001145638.3 | c.839G>A | p.Arg280Gln | missense_variant | 7/14 | ENST00000440944.6 | |
GPSM1 | NM_015597.6 | c.839G>A | p.Arg280Gln | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPSM1 | ENST00000440944.6 | c.839G>A | p.Arg280Gln | missense_variant | 7/14 | 5 | NM_001145638.3 | P1 | |
GPSM1 | ENST00000616132.4 | c.839G>A | p.Arg280Gln | missense_variant | 7/9 | 1 | |||
GPSM1 | ENST00000354753.7 | c.935G>A | p.Arg312Gln | missense_variant | 7/14 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 34
GnomAD3 genomes
AF:
AC:
6
AN:
152214
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000818 AC: 20AN: 244382Hom.: 0 AF XY: 0.000113 AC XY: 15AN XY: 132956
GnomAD3 exomes
AF:
AC:
20
AN:
244382
Hom.:
AF XY:
AC XY:
15
AN XY:
132956
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000953 AC: 139AN: 1458928Hom.: 1 Cov.: 32 AF XY: 0.000105 AC XY: 76AN XY: 725588
GnomAD4 exome
AF:
AC:
139
AN:
1458928
Hom.:
Cov.:
32
AF XY:
AC XY:
76
AN XY:
725588
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74360
GnomAD4 genome
AF:
AC:
6
AN:
152214
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
10
EpiCase
AF:
EpiControl
AF:
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 | Aug 17, 2022 | The c.839G>A (p.R280Q) alteration is located in exon 7 (coding exon 7) of the GPSM1 gene. This alteration results from a G to A substitution at nucleotide position 839, causing the arginine (R) at amino acid position 280 to be replaced by a glutamine (Q). 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
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0409);Loss of MoRF binding (P = 0.0409);.;
MVP
MPC
0.55
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at