6-32192154-G-T

Variant names:

• chr6-32192154-G-T
• rs148125791
• NM_001276501.2:c.139C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001276501.2(GPSM3):​c.139C>A​(p.His47Asn) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPSM3 NM_001276501.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055239946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM3	NM_001276501.2	c.139C>A	p.His47Asn	missense_variant	Exon 2 of 4	ENST00000375040.8	NP_001263430.1
GPSM3	NM_022107.3	c.139C>A	p.His47Asn	missense_variant	Exon 6 of 8		NP_071390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM3	ENST00000375040.8	c.139C>A	p.His47Asn	missense_variant	Exon 2 of 4	1	NM_001276501.2	ENSP00000364180.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.37e-7 AC: 1 AN: 1357698 Hom.: 0 Cov.: 30 AF XY: 0.00000151 AC XY: 1 AN XY: 664226

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: 0.0000202

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000871 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.60
DEOGEN2	Benign	0.0059	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.48	T;.;.
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.26	.;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.19	N;N;N
REVEL	Benign	0.019
Sift	Benign	0.30	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.15
MutPred		0.27		.;Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.043
MPC		0.48
ClinPred		0.065	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.042
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148125791; hg19: chr6-32159931;