Variant 9-136334629-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.251G>A(p.Arg84Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,612,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

GPSM1
NM_001145638.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

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 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=0.22165653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM1	NM_001145638.3 linkuse as main transcript	c.251G>A	p.Arg84Gln	missense_variant	2/14	ENST00000440944.6
GPSM1	NM_015597.6 linkuse as main transcript	c.251G>A	p.Arg84Gln	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPSM1	ENST00000440944.6 linkuse as main transcript	c.251G>A	p.Arg84Gln	missense_variant	2/14	5	NM_001145638.3	P1
GPSM1	ENST00000616132.4 linkuse as main transcript	c.251G>A	p.Arg84Gln	missense_variant	2/9	1
GPSM1	ENST00000354753.7 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	2/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250056

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460206

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

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

Jan 30, 2024

The c.251G>A (p.R84Q) alteration is located in exon 2 (coding exon 2) of the GPSM1 gene. This alteration results from a G to A substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Benign

0.46

Sift4G

Benign

0.083

T;T;.

Vest4

0.24

MutPred

0.42

Gain of methylation at K80 (P = 0.082);Gain of methylation at K80 (P = 0.082);.;

MVP

0.88

MPC

0.18

ClinPred

0.34

GERP RS

3.5

gMVP

0.16

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