Variant 9-136327736-G-A 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_001145638.3(GPSM1):c.41G>A(p.Gly14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,193,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

GPSM1
NM_001145638.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.624

Variant links:

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]

GPSM1 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=0.2324957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPSM1	NM_001145638.3 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/14	ENST00000440944.6	NP_001139110.2
GPSM1	NM_015597.6 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/9		NP_056412.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPSM1	ENST00000440944.6 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/14	5	NM_001145638.3	ENSP00000392828	P1
GPSM1	ENST00000616132.4 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/9	1		ENSP00000479405

Frequencies

GnomAD3 genomes

AF:

0.000173

AC:

AN:

150564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000393

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000238

Gnomad OTH

AF:

0.000964

GnomAD4 exome

AF:

0.000187

AC:

195

AN:

1043200

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

105

AN XY:

497596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000587

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000173

AC:

AN:

150672

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73590

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000393

Gnomad4 NFE

AF:

0.000238

Gnomad4 OTH

AF:

0.000954

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000147

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

Apr 01, 2024

The c.41G>A (p.G14D) alteration is located in exon 1 (coding exon 1) of the GPSM1 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the glycine (G) at amino acid position 14 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.54

T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

-0.18

MutationTaster

Benign

0.99

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.28

.;N

REVEL

Uncertain

0.53

Sift

Benign

0.054

.;T

Sift4G

Benign

0.17

T;T

Vest4

0.16

MutPred

0.20

Loss of methylation at R18 (P = 0.1938);Loss of methylation at R18 (P = 0.1938);

MVP

0.90

MPC

0.20

ClinPred

0.099

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.32

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.

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