6-32191833-G-A

Variant names:

• chr6-32191833-G-A
• rs780898047
• NM_001276501.2:c.221C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001276501.2(GPSM3):​c.221C>T​(p.Ser74Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000445 in 1,460,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: GPSM3 NM_001276501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22236311).

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.221C>T	p.Ser74Phe	missense	Exon 3 of 4	NP_001263430.1	Q9Y4H4
	GPSM3	NM_022107.3		c.221C>T	p.Ser74Phe	missense	Exon 7 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.221C>T	p.Ser74Phe	missense	Exon 3 of 4	ENSP00000364180.3	Q9Y4H4
	GPSM3	ENST00000375043.3	TSL:1	c.221C>T	p.Ser74Phe	missense	Exon 7 of 8	ENSP00000364183.3	Q9Y4H4
	GPSM3	ENST00000874270.1		c.221C>T	p.Ser74Phe	missense	Exon 4 of 5	ENSP00000544329.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245314 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1460322 Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42 AN XY: 726508

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111868

Other (OTH) AF: 0.0000166 AC: 1 AN: 60332

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.0000169 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T
PhyloP100		2.3
Vest4		0.23
MVP		0.41
ClinPred		0.80	D
GERP RS		4.2
Varity_R		0.18
Mutation Taster		=86/14	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: rs780898047; hg19: chr6-32159610; COSMIC: COSV66679958; COSMIC: COSV66679958;