6-32191833-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.221C>T​(p.Ser74Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000445 in 1,460,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

GPSM3
NM_001276501.2 missense

Scores

2
4
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31
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=0.22236311).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPSM3NM_001276501.2 linkuse as main transcriptc.221C>T p.Ser74Phe missense_variant 3/4 ENST00000375040.8 NP_001263430.1
GPSM3NM_022107.3 linkuse as main transcriptc.221C>T p.Ser74Phe 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.221C>T p.Ser74Phe missense_variant 3/41 NM_001276501.2 ENSP00000364180 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000163
AC:
4
AN:
245314
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134082
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000101
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000182
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000445
AC:
65
AN:
1460322
Hom.:
0
Cov.:
32
AF XY:
0.0000578
AC XY:
42
AN XY:
726508
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000468
Hom.:
0
ExAC
AF:
0.0000169
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsMay 30, 2023The c.221C>T (p.S74F) 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 221, causing the serine (S) at amino acid position 74 to be replaced by a phenylalanine (F). 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
0.66
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
29
DANN
Uncertain
1.0
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.87
D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.22
T
MutationTaster
Benign
0.99
D;D;D
Vest4
0.23
MVP
0.41
ClinPred
0.80
D
GERP RS
4.2

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: rs780898047; hg19: chr6-32159610; COSMIC: COSV66679958; COSMIC: COSV66679958; API