5-151794222-G-C

Variant names:

• chr5-151794222-G-C
• rs1762708962
• NM_005754.3:c.415G>C

Variant summary

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

The NM_005754.3(G3BP1):​c.415G>C​(p.Gly139Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G139C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: G3BP1 NM_005754.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.54
• Publications: 0 publications found

Genes affected

G3BP1 (HGNC:30292): (G3BP stress granule assembly factor 1) This gene encodes one of the DNA-unwinding enzymes which prefers partially unwound 3'-tailed substrates and can also unwind partial RNA/DNA and RNA/RNA duplexes in an ATP-dependent fashion. This enzyme is a member of the heterogeneous nuclear RNA-binding proteins and is also an element of the Ras signal transduction pathway. It binds specifically to the Ras-GTPase-activating protein by associating with its SH3 domain. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G3BP1	NM_005754.3	c.415G>C	p.Gly139Arg	missense_variant	Exon 5 of 12	ENST00000356245.8	NP_005745.1
G3BP1	NM_198395.2	c.415G>C	p.Gly139Arg	missense_variant	Exon 5 of 12		NP_938405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G3BP1	ENST00000356245.8	c.415G>C	p.Gly139Arg	missense_variant	Exon 5 of 12	1	NM_005754.3	ENSP00000348578.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457218 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 725312

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107888

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	2.9	M;M
PhyloP100		6.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.98	D;D
Vest4		0.48
MutPred		0.34		Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);
MVP		0.67
MPC		1.4
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.24
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1762708962; hg19: chr5-151173783;