chr5-151786705-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005754.3(G3BP1):​c.85A>G​(p.Met29Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

G3BP1
NM_005754.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Publications

0 publications found
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31586933).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
G3BP1NM_005754.3 linkc.85A>G p.Met29Val missense_variant Exon 2 of 12 ENST00000356245.8 NP_005745.1 Q13283-1Q5U0Q1Q6ZP53
G3BP1NM_198395.2 linkc.85A>G p.Met29Val missense_variant Exon 2 of 12 NP_938405.1 Q13283-1Q5U0Q1Q6ZP53

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
G3BP1ENST00000356245.8 linkc.85A>G p.Met29Val missense_variant Exon 2 of 12 1 NM_005754.3 ENSP00000348578.3 Q13283-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449904
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
722090
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33256
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26086
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39646
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
85994
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1101070
Other (OTH)
AF:
0.00
AC:
0
AN:
59978
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.85A>G (p.M29V) alteration is located in exon 2 (coding exon 1) of the G3BP1 gene. This alteration results from a A to G substitution at nucleotide position 85, causing the methionine (M) at amino acid position 29 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
0.48
BayesDel_addAF
Benign
-0.026
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.027
.;T;T;T;.;T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.065
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.77
T;T;.;T;T;T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.32
T;T;T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.0
.;.;L;L;.;.;.
PhyloP100
5.2
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;.
REVEL
Benign
0.13
Sift
Benign
0.27
T;T;T;T;T;T;.
Sift4G
Benign
0.45
T;T;T;T;T;T;T
Polyphen
0.0040
.;.;B;B;.;.;.
Vest4
0.31, 0.36, 0.25
MutPred
0.46
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
0.68
MPC
0.46
ClinPred
0.59
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.41
gMVP
0.26
Mutation Taster
=74/26
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

Publications

Other links and lift over

hg19: chr5-151166266; API