Variant 9-136340958-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145638.3(GPSM1):c.1172C>T(p.Ser391Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,562,342 control chromosomes in the GnomAD database, including 44,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4473 hom., cov: 32)

Exomes 𝑓: 0.24 ( 40511 hom. )

Consequence

GPSM1
NM_001145638.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046917796).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPSM1	NM_001145638.3 linkuse as main transcript	c.1172C>T	p.Ser391Leu	missense_variant	9/14	ENST00000440944.6	NP_001139110.2
GPSM1	NM_015597.6 linkuse as main transcript	c.1172C>T	p.Ser391Leu	missense_variant	9/9		NP_056412.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GPSM1	ENST00000440944.6 linkuse as main transcript	c.1172C>T	p.Ser391Leu	missense_variant	9/14	5	NM_001145638.3	ENSP00000392828	P1
GPSM1	ENST00000616132.4 linkuse as main transcript	c.1172C>T	p.Ser391Leu	missense_variant	9/9	1		ENSP00000479405
GPSM1	ENST00000354753.7 linkuse as main transcript	c.1268C>T	p.Ser423Leu	missense_variant	9/14	5		ENSP00000346797

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36180

AN:

151922

Hom.:

4469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.226

AC:

38262

AN:

169134

Hom.:

4662

AF XY:

0.220

AC XY:

19979

AN XY:

90656

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.0390

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.236

AC:

333441

AN:

1410302

Hom.:

40511

Cov.:

AF XY:

0.234

AC XY:

163226

AN XY:

696934

show subpopulations

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.0895

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.228

GnomAD4 genome

AF:

0.238

AC:

36217

AN:

152040

Hom.:

4473

Cov.:

AF XY:

0.236

AC XY:

17566

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.0511

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.241

Hom.:

4149

Bravo

AF:

0.235

TwinsUK

AF:

0.247

AC:

916

ALSPAC

AF:

0.252

AC:

972

ESP6500AA

AF:

0.220

AC:

940

ESP6500EA

AF:

0.235

AC:

1981

ExAC

AF:

0.173

AC:

19770

Asia WGS

AF:

0.142

AC:

494

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

.;N;.

REVEL

Benign

0.21

Sift

Benign

0.082

.;T;.

Sift4G

Benign

0.38

T;T;.

Vest4

0.086

MPC

0.14

ClinPred

0.0031

GERP RS

1.9

gMVP

0.33

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over