chrX-133536143-A-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_004484.4(GPC3):c.1724T>G(p.Phe575Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,094,065 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. F575F) has been classified as Likely benign.
Frequency
Consequence
NM_004484.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.1724T>G | p.Phe575Cys | missense_variant | 8/8 | ENST00000370818.8 | |
GPC3 | NM_001164617.2 | c.1793T>G | p.Phe598Cys | missense_variant | 9/9 | ||
GPC3 | NM_001164618.2 | c.1676T>G | p.Phe559Cys | missense_variant | 8/8 | ||
GPC3 | NM_001164619.2 | c.1562T>G | p.Phe521Cys | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.1724T>G | p.Phe575Cys | missense_variant | 8/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1094065Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 1AN XY: 360185
GnomAD4 genome ? Cov.: 21
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2019 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/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 | Aug 05, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at