rs61754633
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004484.4(GPC3):āc.876T>Gā(p.Ile292Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,666 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I292T) has been classified as Uncertain significance.
Frequency
Consequence
NM_004484.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.876T>G | p.Ile292Met | missense_variant | 3/8 | ENST00000370818.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.876T>G | p.Ile292Met | missense_variant | 3/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.0000327 AC: 6AN: 183334Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67814
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097666Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 363036
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2022 | This variant is present in population databases (rs61754633, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 292 of the GPC3 protein (p.Ile292Met). This variant has not been reported in the literature in individuals affected with GPC3-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GPC3 protein function. ClinVar contains an entry for this variant (Variation ID: 843877). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at