rs12663103

Variant names:

• chr6-32193547-T-C
• rs12663103
• ENST00000375043.3:c.-101-423A>G

Variant summary

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

The ENST00000375043.3(GPSM3):​c.-101-423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,210 control chromosomes in the GnomAD database, including 344 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 0.062 (344 hom., cov: 32)
• Consequence: GPSM3 ENST00000375043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921
• Publications: 27 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM3	NM_022107.3	c.-101-423A>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.-101-423A>G		intron_variant	Intron 3 of 7	1		ENSP00000364183.3

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9368 AN: 152092 Hom.: 346 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0506

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0662

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

GnomAD4 genome AF: 0.0615 AC: 9366 AN: 152210 Hom.: 344 Cov.: 32 AF XY: 0.0604 AC XY: 4497 AN XY: 74444

African (AFR) AF: 0.0814 AC: 3378 AN: 41514

American (AMR) AF: 0.0505 AC: 772 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.0463 AC: 240 AN: 5180

South Asian (SAS) AF: 0.0983 AC: 474 AN: 4820

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0566 AC: 3851 AN: 68014

Other (OTH) AF: 0.0655 AC: 138 AN: 2106

Alfa AF: 0.0560 Hom.: 737

Bravo AF: 0.0649

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.76
PhyloP100		0.92
PromoterAI		0.017	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: rs12663103; hg19: chr6-32161324;