Genetic Variant NM_001276501.2:c.139C>G (chr6-32192154-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001276501.2(GPSM3):c.139C>G(p.His47Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 1,509,708 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0067 ( 91 hom. )

Consequence

GPSM3
NM_001276501.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.980

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004505217).

BP6

Variant 6-32192154-G-C is Benign according to our data. Variant chr6-32192154-G-C is described in ClinVar as Benign. ClinVar VariationId is 772877.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM3	NM_001276501.2	MANE Select	c.139C>G	p.His47Asp	missense	Exon 2 of 4	NP_001263430.1	Q9Y4H4
	GPSM3	NM_022107.3		c.139C>G	p.His47Asp	missense	Exon 6 of 8	NP_071390.1	Q9Y4H4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPSM3	ENST00000375040.8	TSL:1 MANE Select	c.139C>G	p.His47Asp	missense	Exon 2 of 4	ENSP00000364180.3	Q9Y4H4
GPSM3	ENST00000375043.3	TSL:1	c.139C>G	p.His47Asp	missense	Exon 6 of 8	ENSP00000364183.3	Q9Y4H4
GPSM3	ENST00000874270.1		c.139C>G	p.His47Asp	missense	Exon 3 of 5	ENSP00000544329.1

Frequencies

GnomAD3 genomes

AF:

0.00706

AC:

1072

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.00590

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.00655

AC:

1139

AN:

173834

AF XY:

0.00687

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.00571

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00657

Gnomad OTH exome

AF:

0.00796

GnomAD4 exome

AF:

0.00669

AC:

9083

AN:

1357652

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

4613

AN XY:

664208

show subpopulations

African (AFR)

AF:

0.00865

AC:

260

AN:

30046

American (AMR)

AF:

0.00665

AC:

190

AN:

28556

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

400

AN:

19734

East Asian (EAS)

AF:

0.000756

AC:

AN:

38368

South Asian (SAS)

AF:

0.0117

AC:

811

AN:

69370

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

49540

Middle Eastern (MID)

AF:

0.0808

AC:

415

AN:

5138

European-Non Finnish (NFE)

AF:

0.00604

AC:

6407

AN:

1061130

Other (OTH)

AF:

0.00891

AC:

497

AN:

55770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

443

887

1330

1774

2217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00701

AC:

1066

AN:

152056

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

536

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00878

AC:

364

AN:

41468

American (AMR)

AF:

0.00758

AC:

116

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3472

East Asian (EAS)

AF:

0.00175

AC:

AN:

5156

South Asian (SAS)

AF:

0.00912

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00590

AC:

401

AN:

67926

Other (OTH)

AF:

0.0180

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

113

170

226

283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00619

Hom.:

Bravo

AF:

0.00725

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00651

AC:

748

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.014

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.98

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.090

REVEL

Benign

0.023

Sift

Benign

0.084

Sift4G

Benign

0.83

Polyphen

0.0010

Vest4

0.30

MVP

0.043

MPC

0.62

ClinPred

0.0016

GERP RS

1.8

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.072

gMVP

0.20

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over