rs763327506
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The ENST00000370818.8(GPC3):āc.856A>Gā(p.Met286Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000082 in 1,097,952 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
ENST00000370818.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.856A>G | p.Met286Val | missense_variant | 3/8 | ENST00000370818.8 | NP_004475.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.856A>G | p.Met286Val | missense_variant | 3/8 | 1 | NM_004484.4 | ENSP00000359854 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183287Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67787
GnomAD4 exome AF: 0.00000820 AC: 9AN: 1097952Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 3AN XY: 363320
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 10, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 286 of the GPC3 protein (p.Met286Val). This variant is present in population databases (rs763327506, gnomAD 0.006%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with GPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 568197). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GPC3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at