rs1300949168

Variant names:

• chr9-136327712-C-A
• NM_001145638.3:c.17C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-136327712-C-A
• chr9-136327712-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145638.3(GPSM1):​c.17C>A​(p.Pro6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000983 in 1,017,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
• Consequence: GPSM1 NM_001145638.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28860384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM1	NM_001145638.3	c.17C>A	p.Pro6Gln	missense_variant	Exon 1 of 14	ENST00000440944.6	NP_001139110.2
GPSM1	NM_015597.6	c.17C>A	p.Pro6Gln	missense_variant	Exon 1 of 9		NP_056412.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM1	ENST00000440944.6	c.17C>A	p.Pro6Gln	missense_variant	Exon 1 of 14	5	NM_001145638.3	ENSP00000392828.1
GPSM1	ENST00000616132.4	c.17C>A	p.Pro6Gln	missense_variant	Exon 1 of 9	1		ENSP00000479405.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.83e-7 AC: 1 AN: 1017672 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 484642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000113

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.97
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.51	T;T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Uncertain	0.13	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.38	.;N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.0030	D;D
Vest4		0.17
MutPred		0.20		Loss of glycosylation at P6 (P = 0.0771);Loss of glycosylation at P6 (P = 0.0771);
MVP		0.97
MPC		0.14
ClinPred		0.38	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139222168;