chr9-136327712-C-T

Variant names:

• chr9-136327712-C-T
• rs1300949168
• NM_001145638.3:c.17C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145638.3(GPSM1):​c.17C>T​(p.Pro6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,017,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPSM1 NM_001145638.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.122
• Publications: 0 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]

DKFZP434A062 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2656249).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145638.3. 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
	GPSM1	NM_001145638.3	MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 14	NP_001139110.2	A0A0A0MSK4
	GPSM1	NM_015597.6		c.17C>T	p.Pro6Leu	missense	Exon 1 of 9	NP_056412.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM1	ENST00000440944.6	TSL:5 MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 14	ENSP00000392828.1	A0A0A0MSK4
	GPSM1	ENST00000616132.4	TSL:1	c.17C>T	p.Pro6Leu	missense	Exon 1 of 9	ENSP00000479405.1	A0A087WVF5
	DKFZP434A062	ENST00000848857.1		n.-70G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149926 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2792 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000197 AC: 2 AN: 1017672 Hom.: 0 Cov.: 21 AF XY: 0.00000206 AC XY: 1 AN XY: 484642

African (AFR) AF: 0.00 AC: 0 AN: 20190

American (AMR) AF: 0.00 AC: 0 AN: 6680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11448

East Asian (EAS) AF: 0.00 AC: 0 AN: 19420

South Asian (SAS) AF: 0.00 AC: 0 AN: 20088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2620

European-Non Finnish (NFE) AF: 0.00000227 AC: 2 AN: 881362

Other (OTH) AF: 0.00 AC: 0 AN: 38662

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149926 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73090

African (AFR) AF: 0.00 AC: 0 AN: 41190

American (AMR) AF: 0.00 AC: 0 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67076

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.027	T
PhyloP100		0.12
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.75	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Vest4		0.15
MutPred		0.21		Loss of glycosylation at P6 (P = 0.0771)
MVP		0.72
MPC		0.16
ClinPred		0.47	T
GERP RS		1.9
PromoterAI		0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.18
Mutation Taster		=95/5	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: rs1300949168; hg19: chr9-139222168;