chr9-136340958-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145638.3(GPSM1):​c.1172C>G​(p.Ser391*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPSM1 NM_001145638.3 stop_gained
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM1	NM_001145638.3	c.1172C>G	p.Ser391*	stop_gained	Exon 9 of 14	ENST00000440944.6	NP_001139110.2
GPSM1	NM_015597.6	c.1172C>G	p.Ser391*	stop_gained	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>G	p.Ser391*	stop_gained	Exon 9 of 14	5	NM_001145638.3	ENSP00000392828.1
GPSM1	ENST00000616132.4	c.1172C>G	p.Ser391*	stop_gained	Exon 9 of 9	1		ENSP00000479405.1
GPSM1	ENST00000354753.7	c.1268C>G	p.Ser423*	stop_gained	Exon 9 of 14	5		ENSP00000346797.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.14	N
PhyloP100		-0.0030
Vest4		0.41
GERP RS		1.9
Mutation Taster		=28/172	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;