9-136340958-C-T

Variant names:

• chr9-136340958-C-T
• rs60980157
• NM_001145638.3:c.1172C>T

Variant summary

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

The NM_001145638.3(GPSM1):​c.1172C>T​(p.Ser391Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,562,342 control chromosomes in the GnomAD database, including 44,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4473 hom., cov: 32)
  • Exomes 𝑓: 0.24 (40511 hom.)
• Consequence: GPSM1 NM_001145638.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 40 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046917796).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM1	NM_001145638.3	c.1172C>T	p.Ser391Leu	missense_variant	Exon 9 of 14	ENST00000440944.6	NP_001139110.2
GPSM1	NM_015597.6	c.1172C>T	p.Ser391Leu	missense_variant	Exon 9 of 9		NP_056412.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM1	ENST00000440944.6	c.1172C>T	p.Ser391Leu	missense_variant	Exon 9 of 14	5	NM_001145638.3	ENSP00000392828.1
GPSM1	ENST00000616132.4	c.1172C>T	p.Ser391Leu	missense_variant	Exon 9 of 9	1		ENSP00000479405.1
GPSM1	ENST00000354753.7	c.1268C>T	p.Ser423Leu	missense_variant	Exon 9 of 14	5		ENSP00000346797.4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36180 AN: 151922 Hom.: 4469 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.226 AC: 38262 AN: 169134 AF XY: 0.220

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0390

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.236 AC: 333441 AN: 1410302 Hom.: 40511 Cov.: 36 AF XY: 0.234 AC XY: 163226 AN XY: 696934

African (AFR) AF: 0.236 AC: 7604 AN: 32244

American (AMR) AF: 0.264 AC: 9898 AN: 37434

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5710 AN: 25202

East Asian (EAS) AF: 0.0895 AC: 3302 AN: 36878

South Asian (SAS) AF: 0.184 AC: 14776 AN: 80128

European-Finnish (FIN) AF: 0.300 AC: 14554 AN: 48490

Middle Eastern (MID) AF: 0.189 AC: 1043 AN: 5506

European-Non Finnish (NFE) AF: 0.242 AC: 263231 AN: 1086066

Other (OTH) AF: 0.228 AC: 13323 AN: 58354

GnomAD4 genome AF: 0.238 AC: 36217 AN: 152040 Hom.: 4473 Cov.: 32 AF XY: 0.236 AC XY: 17566 AN XY: 74312

African (AFR) AF: 0.231 AC: 9570 AN: 41480

American (AMR) AF: 0.265 AC: 4049 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3472

East Asian (EAS) AF: 0.0511 AC: 264 AN: 5164

South Asian (SAS) AF: 0.168 AC: 810 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3111 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16799 AN: 67936

Other (OTH) AF: 0.234 AC: 493 AN: 2106

Alfa AF: 0.241 Hom.: 5648

Bravo AF: 0.235

TwinsUK AF: 0.247 AC: 916

ESP6500AA AF: 0.220 AC: 940

ESP6500EA AF: 0.235 AC: 1981

ExAC AF: 0.173 AC: 19770

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0	.;.;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.82
LIST_S2	Benign	0.71	T;T;T
MetaRNN	Benign	0.0047	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.;.
PhyloP100		-0.0030
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.0	.;N;.
Sift	Pathogenic	0.0	.;T;.
Sift4G	Benign	0.38	T;T;.
Vest4		0.086
ClinPred		0.0031	T
GERP RS		1.9
gMVP		0.33
Mutation Taster		=96/4	polymorphism (auto)

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: rs60980157; hg19: chr9-139235415; COSMIC: COSV61305908;