ENST00000375043.3:c.-102+235C>T

Variant names:

• chr6-32194075-G-A
• rs204989
• ENST00000375043.3:c.-102+235C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000375043.3(GPSM3):​c.-102+235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,154 control chromosomes in the GnomAD database, including 3,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3588 hom., cov: 32)
• Consequence: GPSM3 ENST00000375043.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.116

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-32194075-G-A is Benign according to our data. Variant chr6-32194075-G-A is described in ClinVar as [Benign]. Clinvar id is 1294559.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.-102+235C>T		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.-102+235C>T		intron_variant	Intron 3 of 7	1		ENSP00000364183.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31832 AN: 152034 Hom.: 3594 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.301

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: 0.209 AC: 31843 AN: 152154 Hom.: 3588 Cov.: 32 AF XY: 0.204 AC XY: 15205 AN XY: 74366

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.189

Alfa AF: 0.210 Hom.: 1168

Bravo AF: 0.213

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26821282) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs204989; hg19: chr6-32161852;