Variant chr6-32192473-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001276501.2(GPSM3):c.41A>C(p.Gln14Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000695 in 1,438,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GPSM3
NM_001276501.2 missense, splice_region

Scores

Splicing: ADA: 0.7410

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

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]

GPSM3 links:

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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=0.22067401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM3	NM_001276501.2 linkuse as main transcript	c.41A>C	p.Gln14Pro	missense_variant, splice_region_variant	1/4	ENST00000375040.8
GPSM3	NM_022107.3 linkuse as main transcript	c.41A>C	p.Gln14Pro	missense_variant, splice_region_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM3	ENST00000375040.8 linkuse as main transcript	c.41A>C	p.Gln14Pro	missense_variant, splice_region_variant	1/4	1	NM_001276501.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1438654

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713290

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Dec 21, 2022

The c.41A>C (p.Q14P) alteration is located in exon 5 (coding exon 1) of the GPSM3 gene. This alteration results from a A to C substitution at nucleotide position 41, causing the glutamine (Q) at amino acid position 14 to be replaced by a proline (P). 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

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.019

T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.016

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.40

MutPred

0.17

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.18

MPC

0.53

ClinPred

0.77

GERP RS

3.2

Varity_R

0.15

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.74

dbscSNV1_RF

Benign

0.46

SpliceAI score (max)

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over