NM_005754.3:c.263A>T

Variant names:

• chr5-151790974-A-T
• rs1762642916
• NM_005754.3:c.263A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005754.3(G3BP1):​c.263A>T​(p.Asp88Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D88G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: G3BP1 NM_005754.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.11
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G3BP1	NM_005754.3	c.263A>T	p.Asp88Val	missense_variant	Exon 4 of 12	ENST00000356245.8	NP_005745.1
G3BP1	NM_198395.2	c.263A>T	p.Asp88Val	missense_variant	Exon 4 of 12		NP_938405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G3BP1	ENST00000356245.8	c.263A>T	p.Asp88Val	missense_variant	Exon 4 of 12	1	NM_005754.3	ENSP00000348578.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;T;D;D;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;.;D;D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Pathogenic	3.0	.;.;M;M;.;.
PhyloP100		9.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0030	D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D
Polyphen		0.11	.;.;B;B;.;.
Vest4		0.75, 0.69
MutPred		0.72		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;Loss of sheet (P = 0.1907);
MVP		0.77
MPC		1.1
ClinPred		0.99	D
GERP RS		4.7
PromoterAI		-0.015	Neutral
Varity_R		0.80
gMVP		0.51
Mutation Taster		=191/109	polymorphism

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

Other links and lift over

dbSNP: rs1762642916; hg19: chr5-151170535;