rs3812550

Positions:

• chr9-136358427-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145638.3(GPSM1):​c.*207A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 577,946 control chromosomes in the GnomAD database, including 59,488 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 0.43 (14246 hom., cov: 35)
  • Exomes 𝑓: 0.45 (45242 hom.)
• Consequence: GPSM1 NM_001145638.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.49

Genes affected

GPSM1 (HGNC:17858): (G protein signaling modulator 1) G-protein signaling modulators (GPSMs) play diverse functional roles through their interaction with G-protein subunits. This gene encodes a receptor-independent activator of G protein signaling, which is one of several factors that influence the basal activity of G-protein signaling systems. The protein contains seven tetratricopeptide repeats in its N-terminal half and four G-protein regulatory (GPR) motifs in its C-terminal half. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPSM1	NM_001145638.3	c.*207A>G		3_prime_UTR_variant	14/14	ENST00000440944.6	NP_001139110.2
GPSM1	NM_001145639.2	c.*207A>G		3_prime_UTR_variant	4/4		NP_001139111.1
GPSM1	NM_001200003.2	c.*207A>G		3_prime_UTR_variant	4/4		NP_001186932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPSM1	ENST00000440944.6	c.*207A>G		3_prime_UTR_variant	14/14	5	NM_001145638.3	ENSP00000392828	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64598 AN: 151962 Hom.: 14231 Cov.: 35

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.455 AC: 193700 AN: 425866 Hom.: 45242 Cov.: 4 AF XY: 0.449 AC XY: 101295 AN XY: 225406

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.425 AC: 64651 AN: 152080 Hom.: 14246 Cov.: 35 AF XY: 0.423 AC XY: 31419 AN XY: 74334

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.405

Alfa AF: 0.462 Hom.: 2598

Bravo AF: 0.421

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.015
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs3812550; hg19: chr9-139252879;