4-75645590-T-C

Position:

• chr4-75645590-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_203505.3(G3BP2):​c.1289A>G​(p.Asn430Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000034 (0 hom.)
• Consequence: G3BP2 NM_203505.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521

Genes affected

G3BP2 (HGNC:30291): (G3BP stress granule assembly factor 2) Enables RNA binding activity. Involved in positive regulation of stress granule assembly and protein homooligomerization. Located in cytoplasmic stress granule and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050961673).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G3BP2	NM_203505.3	c.1289A>G	p.Asn430Ser	missense_variant	12/12	ENST00000359707.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G3BP2	ENST00000359707.9	c.1289A>G	p.Asn430Ser	missense_variant	12/12	1	NM_203505.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251416 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135874

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727246

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: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.4
DANN	Benign	0.67
DEOGEN2	Benign	0.13	T;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.46	N
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.051	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L;L;.
MutationTaster	Benign	0.91	D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.049
MutPred		0.32		Loss of stability (P = 0.0468);Loss of stability (P = 0.0468);.;
MVP		0.36
MPC		0.91
ClinPred		0.018	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.046
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs754378203; hg19: chr4-76570774;