chr6-32192168-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.125C>T​(p.Pro42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,510,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

GPSM3
NM_001276501.2 missense

Scores

10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
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=0.103548616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPSM3NM_001276501.2 linkuse as main transcriptc.125C>T p.Pro42Leu missense_variant 2/4 ENST00000375040.8 NP_001263430.1
GPSM3NM_022107.3 linkuse as main transcriptc.125C>T p.Pro42Leu 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.125C>T p.Pro42Leu missense_variant 2/41 NM_001276501.2 ENSP00000364180 P1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151952
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
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:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000689
AC:
12
AN:
174138
Hom.:
0
AF XY:
0.0000655
AC XY:
6
AN XY:
91610
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000655
AC:
89
AN:
1359030
Hom.:
0
Cov.:
30
AF XY:
0.0000662
AC XY:
44
AN XY:
664946
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:
0.0000144
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000819
Gnomad4 OTH exome
AF:
0.0000179
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151952
Hom.:
0
Cov.:
31
AF XY:
0.0000270
AC XY:
2
AN XY:
74192
show subpopulations
Gnomad4 AFR
AF:
0.0000484
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:
0.0000736
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000742
Hom.:
0
ExAC
AF:
0.0000870
AC:
10

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 GeneticsApr 24, 2024The c.125C>T (p.P42L) 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 125, causing the proline (P) at amino acid position 42 to be replaced by a leucine (L). 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
0.072
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Benign
0.71
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.54
D
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.10
T
MutationTaster
Benign
0.98
D;D;D
Vest4
0.36
MVP
0.12
ClinPred
0.087
T
GERP RS
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs767769979; hg19: chr6-32159945; API