ENST00000375043.3:c.-101-465A>G

Variant names:

• chr6-32193589-T-C
• rs204991
• ENST00000375043.3:c.-101-465A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375043.3(GPSM3):​c.-101-465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,998 control chromosomes in the GnomAD database, including 3,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3597 hom., cov: 32)
• Consequence: GPSM3 ENST00000375043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 61 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM3	NM_022107.3	c.-101-465A>G		intron_variant	Intron 3 of 7		NP_071390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM3	ENST00000375043.3	c.-101-465A>G		intron_variant	Intron 3 of 7	1		ENSP00000364183.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31893 AN: 151880 Hom.: 3603 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31904 AN: 151998 Hom.: 3597 Cov.: 32 AF XY: 0.205 AC XY: 15249 AN XY: 74294

African (AFR) AF: 0.271 AC: 11242 AN: 41424

American (AMR) AF: 0.156 AC: 2384 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 564 AN: 3472

East Asian (EAS) AF: 0.302 AC: 1556 AN: 5158

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1539 AN: 10544

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13125 AN: 67986

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.205 Hom.: 11977

Bravo AF: 0.214

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.30
PhyloP100		-3.1
PromoterAI		0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs204991; hg19: chr6-32161366;