NM_004484.4:c.355G>T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_004484.4(GPC3):c.355G>T(p.Val119Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar 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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 89522Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 21534 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000237 AC: 221AN: 930592Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 271614
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000223 AC: 2AN: 89555Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 21569
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.V119F variant (also known as c.355G>T), located in coding exon 3 of the GPC3 gene, results from a G to T substitution at nucleotide position 355. The valine at codon 119 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Wilms tumor 1 Uncertain:1
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. ClinVar contains an entry for this variant (Variation ID: 408889). This variant has not been reported in the literature in individuals affected with GPC3-related conditions. 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. This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 119 of the GPC3 protein (p.Val119Phe). 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. -
Simpson-Golabi-Behmel syndrome type 1;CN033288:Wilms tumor 1 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at