6-32192244-G-C

Variant names:

• chr6-32192244-G-C
• rs1004293066
• NM_001276501.2:c.49C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001276501.2(GPSM3):​c.49C>G​(p.Pro17Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 1,370,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: GPSM3 NM_001276501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.123
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059200644).

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.49C>G	p.Pro17Ala	missense	Exon 2 of 4	NP_001263430.1	Q9Y4H4
	GPSM3	NM_022107.3		c.49C>G	p.Pro17Ala	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.49C>G	p.Pro17Ala	missense	Exon 2 of 4	ENSP00000364180.3	Q9Y4H4
	GPSM3	ENST00000375043.3	TSL:1	c.49C>G	p.Pro17Ala	missense	Exon 6 of 8	ENSP00000364183.3	Q9Y4H4
	GPSM3	ENST00000874270.1		c.49C>G	p.Pro17Ala	missense	Exon 3 of 5	ENSP00000544329.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000584 AC: 8 AN: 1370358 Hom.: 0 Cov.: 31 AF XY: 0.00000595 AC XY: 4 AN XY: 672712

African (AFR) AF: 0.00 AC: 0 AN: 30400

American (AMR) AF: 0.00 AC: 0 AN: 30766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20156

East Asian (EAS) AF: 0.00 AC: 0 AN: 38512

South Asian (SAS) AF: 0.00 AC: 0 AN: 71476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.00000749 AC: 8 AN: 1067386

Other (OTH) AF: 0.00 AC: 0 AN: 56370

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.63	N
PhyloP100		0.12
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.060
Sift	Benign	0.29	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.18		Loss of catalytic residue at P16 (P = 0.0131)
MVP		0.068
MPC		0.42
ClinPred		0.077	T
GERP RS		1.3
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.045
gMVP		0.064
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1004293066; hg19: chr6-32160021;