6-32191437-A-C

Variant names:

• chr6-32191437-A-C
• NM_001276501.2:c.412T>G

Variant summary

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

The NM_001276501.2(GPSM3):​c.412T>G​(p.Leu138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,152 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPSM3 NM_001276501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00

Genes affected

GPSM3 (HGNC:13945): (G protein signaling modulator 3) Predicted to enable GTPase regulator activity. Predicted to be involved in positive regulation of inflammatory response. Predicted to act upstream of or within positive regulation of cytokine production involved in inflammatory response and positive regulation of leukocyte chemotaxis. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3194083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM3	NM_001276501.2	c.412T>G	p.Leu138Val	missense_variant	Exon 4 of 4	ENST00000375040.8	NP_001263430.1
GPSM3	NM_022107.3	c.412T>G	p.Leu138Val	missense_variant	Exon 8 of 8		NP_071390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM3	ENST00000375040.8	c.412T>G	p.Leu138Val	missense_variant	Exon 4 of 4	1	NM_001276501.2	ENSP00000364180.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441152 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716332

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.412T>G (p.L138V) alteration is located in exon 8 (coding exon 4) of the GPSM3 gene. This alteration results from a T to G substitution at nucleotide position 412, causing the leucine (L) at amino acid position 138 to be replaced by a valine (V). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.76	T;.;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.99	.;D;D
Vest4		0.48
MutPred		0.61		.;Gain of MoRF binding (P = 0.0801);Gain of MoRF binding (P = 0.0801);
MVP		0.29
MPC		1.3
ClinPred		0.87	D
GERP RS		2.0
Varity_R		0.078
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-32159214;