chr6-32192156-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001276501.2(GPSM3):​c.137G>A​(p.Arg46His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,504,452 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GPSM3
NM_001276501.2 missense

Scores

10

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0360
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054125726).
BP6
Variant 6-32192156-C-T is Benign according to our data. Variant chr6-32192156-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2622643.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPSM3NM_001276501.2 linkuse as main transcriptc.137G>A p.Arg46His missense_variant 2/4 ENST00000375040.8 NP_001263430.1
GPSM3NM_022107.3 linkuse as main transcriptc.137G>A p.Arg46His 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.137G>A p.Arg46His missense_variant 2/41 NM_001276501.2 ENSP00000364180 P1

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151450
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000590
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000117
AC:
2
AN:
170928
Hom.:
0
AF XY:
0.0000222
AC XY:
2
AN XY:
90044
show subpopulations
Gnomad AFR exome
AF:
0.0000674
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000668
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000148
AC:
20
AN:
1353002
Hom.:
0
Cov.:
30
AF XY:
0.00000907
AC XY:
6
AN XY:
661770
show subpopulations
Gnomad4 AFR exome
AF:
0.0000334
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000788
Gnomad4 SAS exome
AF:
0.0000146
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000142
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000264
AC:
4
AN:
151450
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
73890
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000590
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000871
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 12, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
14
DANN
Benign
0.69
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.16
N
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.054
T
MutationTaster
Benign
1.0
N;N;N
Vest4
0.24
MVP
0.16
ClinPred
0.039
T
GERP RS
0.13
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs749245400; hg19: chr6-32159933; API