rs145686781

Variant names:

• chr6-32191414-C-T
• rs145686781
• NM_001276501.2:c.435G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32191414-C-T
• chr6-32191414-C-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001276501.2(GPSM3):​c.435G>A​(p.Gly145Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,593,600 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (10 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (72 hom.)
• Consequence: GPSM3 NM_001276501.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.889
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-32191414-C-T is Benign according to our data. Variant chr6-32191414-C-T is described in ClinVar as Benign. ClinVar VariationId is 770360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.889 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00481 (6938/1441414) while in subpopulation MID AF = 0.0165 (94/5698). AF 95% confidence interval is 0.0151. There are 72 homozygotes in GnomAdExome4. There are 3784 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.435G>A	p.Gly145Gly	synonymous	Exon 4 of 4	NP_001263430.1	Q9Y4H4
	GPSM3	NM_022107.3		c.435G>A	p.Gly145Gly	synonymous	Exon 8 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.435G>A	p.Gly145Gly	synonymous	Exon 4 of 4	ENSP00000364180.3	Q9Y4H4
	GPSM3	ENST00000375043.3	TSL:1	c.435G>A	p.Gly145Gly	synonymous	Exon 8 of 8	ENSP00000364183.3	Q9Y4H4
	GPSM3	ENST00000874270.1		c.435G>A	p.Gly145Gly	synonymous	Exon 5 of 5	ENSP00000544329.1

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152068 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00987

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00500

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00657 AC: 1543 AN: 234894 AF XY: 0.00707

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00744

Gnomad ASJ exome AF: 0.000324

Gnomad EAS exome AF: 0.00743

Gnomad FIN exome AF: 0.00380

Gnomad NFE exome AF: 0.00569

Gnomad OTH exome AF: 0.00689

GnomAD4 exome AF: 0.00481 AC: 6938 AN: 1441414 Hom.: 72 Cov.: 31 AF XY: 0.00528 AC XY: 3784 AN XY: 716870

African (AFR) AF: 0.00119 AC: 38 AN: 32018

American (AMR) AF: 0.00988 AC: 388 AN: 39272

Ashkenazi Jewish (ASJ) AF: 0.000197 AC: 5 AN: 25346

East Asian (EAS) AF: 0.00432 AC: 167 AN: 38656

South Asian (SAS) AF: 0.0158 AC: 1322 AN: 83722

European-Finnish (FIN) AF: 0.00361 AC: 192 AN: 53248

Middle Eastern (MID) AF: 0.0165 AC: 94 AN: 5698

European-Non Finnish (NFE) AF: 0.00378 AC: 4171 AN: 1104018

Other (OTH) AF: 0.00944 AC: 561 AN: 59436

GnomAD4 genome AF: 0.00474 AC: 722 AN: 152186 Hom.: 10 Cov.: 31 AF XY: 0.00464 AC XY: 345 AN XY: 74406

African (AFR) AF: 0.00135 AC: 56 AN: 41522

American (AMR) AF: 0.00824 AC: 126 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00989 AC: 51 AN: 5156

South Asian (SAS) AF: 0.0158 AC: 76 AN: 4818

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00500 AC: 340 AN: 67984

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00396 Hom.: 2

Bravo AF: 0.00426

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.3
DANN	Benign	0.83
PhyloP100		-0.89
Mutation Taster		=100/0	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: rs145686781; hg19: chr6-32159191; COSMIC: COSV66683157; COSMIC: COSV66683157;