chr5-151791009-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_005754.3(G3BP1):c.298A>G(p.Asn100Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
G3BP1
NM_005754.3 missense
NM_005754.3 missense
Scores
6
10
3
Clinical Significance
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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, 0.807
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152120
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461550Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727072 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1461550
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727072
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111800
Other (OTH)
AF:
AC:
0
AN:
60382
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152120
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74312
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41404
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jun 10, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.298A>G (p.N100D) alteration is located in exon 4 (coding exon 3) of the G3BP1 gene. This alteration results from a A to G substitution at nucleotide position 298, causing the asparagine (N) at amino acid position 100 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;D;D;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;.;M;M;.;.
PhyloP100
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;T;D
Polyphen
0.72
.;.;P;P;.;.
Vest4
0.88, 0.82
MutPred
Loss of MoRF binding (P = 0.0924);Loss of MoRF binding (P = 0.0924);Loss of MoRF binding (P = 0.0924);Loss of MoRF binding (P = 0.0924);.;Loss of MoRF binding (P = 0.0924);
MVP
MPC
0.94
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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