rs141100113
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_004484.4(GPC3):c.826G>T(p.Gly276Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,588 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G276S) has been classified as Likely benign.
Frequency
Consequence
NM_004484.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.826G>T | p.Gly276Cys | missense_variant | 3/8 | ENST00000370818.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.826G>T | p.Gly276Cys | missense_variant | 3/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000892 AC: 1AN: 112075Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34249
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183233Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67765
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097513Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1AN XY: 362883
GnomAD4 genome ? AF: 0.00000892 AC: 1AN: 112075Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34249
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; Has not been previously published as pathogenic or benign to our knowledge - |
Wilms tumor 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at