6-32192154-G-C

Variant names:

• chr6-32192154-G-C
• rs148125791
• NM_001276501.2:c.139C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.980
• Publications: 2 publications found

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]

ACMG classification

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

Sel.	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.: 6 Cov.: 31

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

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.: 91 Cov.: 30 AF XY: 0.00695 AC XY: 4613 AN XY: 664208

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: 29 AN: 38368

South Asian (SAS) AF: 0.0117 AC: 811 AN: 69370

European-Finnish (FIN) AF: 0.00149 AC: 74 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

GnomAD4 genome AF: 0.00701 AC: 1066 AN: 152056 Hom.: 6 Cov.: 31 AF XY: 0.00721 AC XY: 536 AN XY: 74326

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: 62 AN: 3472

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5156

South Asian (SAS) AF: 0.00912 AC: 44 AN: 4822

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00590 AC: 401 AN: 67926

Other (OTH) AF: 0.0180 AC: 38 AN: 2106

Alfa AF: 0.00619 Hom.: 1

Bravo AF: 0.00725

ESP6500AA AF: 0.00817 AC: 36

ESP6500EA AF: 0.00686 AC: 59

ExAC AF: 0.00651 AC: 748

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.55
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.98
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.023
Sift	Benign	0.084	T
Sift4G	Benign	0.83	T
Polyphen		0.0010	B
Vest4		0.30
MVP		0.043
MPC		0.62
ClinPred		0.0016	T
GERP RS		1.8
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.072
gMVP		0.20
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs148125791; hg19: chr6-32159931;