9-136336996-G-T

Variant names:

• chr9-136336996-G-T
• rs528339901
• NM_001145638.3:c.502G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145638.3(GPSM1):​c.502G>T​(p.Ala168Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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. A168T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GPSM1 NM_001145638.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08895466).

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.502G>T	p.Ala168Ser	missense	Exon 4 of 14	NP_001139110.2	A0A0A0MSK4
	GPSM1	NM_015597.6		c.502G>T	p.Ala168Ser	missense	Exon 4 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.502G>T	p.Ala168Ser	missense	Exon 4 of 14	ENSP00000392828.1	A0A0A0MSK4
	GPSM1	ENST00000616132.4	TSL:1	c.502G>T	p.Ala168Ser	missense	Exon 4 of 9	ENSP00000479405.1	A0A087WVF5
	GPSM1	ENST00000354753.7	TSL:5	c.598G>T	p.Ala200Ser	missense	Exon 4 of 14	ENSP00000346797.4	A0A0A0MRC4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401578 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 691690

African (AFR) AF: 0.00 AC: 0 AN: 31748

American (AMR) AF: 0.00 AC: 0 AN: 36110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 36082

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081016

Other (OTH) AF: 0.00 AC: 0 AN: 58136

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	2.6
DANN	Benign	0.77
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.60	T
PhyloP100		0.25
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.44	T
Sift4G	Benign	0.52	T
Vest4		0.35
MutPred		0.30		Gain of disorder (P = 0.0315)
MVP		0.83
MPC		0.19
ClinPred		0.22	T
GERP RS		2.8
gMVP		0.27
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs528339901; hg19: chr9-139231453;