9-136336980-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145638.3(GPSM1):c.486A>C(p.Gln162His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPSM1 NM_001145638.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.524

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10896739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM1	NM_001145638.3	c.486A>C	p.Gln162His	missense_variant	4/14	ENST00000440944.6
GPSM1	NM_015597.6	c.486A>C	p.Gln162His	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM1	ENST00000440944.6	c.486A>C	p.Gln162His	missense_variant	4/14	5	NM_001145638.3	P1
GPSM1	ENST00000616132.4	c.486A>C	p.Gln162His	missense_variant	4/9	1
GPSM1	ENST00000354753.7	c.582A>C	p.Gln194His	missense_variant	4/14	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.486A>C (p.Q162H) alteration is located in exon 4 (coding exon 4) of the GPSM1 gene. This alteration results from a A to C substitution at nucleotide position 486, causing the glutamine (Q) at amino acid position 162 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0055	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	15
Dann	Benign	0.82
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.64	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
Sift4G	Benign	0.65	T;T;.
Vest4		0.28
MutPred		0.38		Loss of catalytic residue at Q162 (P = 0.024);Loss of catalytic residue at Q162 (P = 0.024);.;
MVP		0.82
MPC		0.15
ClinPred		0.098	T
GERP RS		2.1
gMVP		0.79

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: chr9-139231437;