chrX-133303069-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001448.3(GPC4):c.1469G>A(p.Ser490Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 111,552 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001448.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC4 | NM_001448.3 | c.1469G>A | p.Ser490Asn | missense_variant, splice_region_variant | 9/9 | ENST00000370828.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC4 | ENST00000370828.4 | c.1469G>A | p.Ser490Asn | missense_variant, splice_region_variant | 9/9 | 1 | NM_001448.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000896 AC: 1AN: 111552Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33760
GnomAD4 exome Cov.: 30
GnomAD4 genome ? AF: 0.00000896 AC: 1AN: 111552Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33760
ClinVar
Submissions by phenotype
GPC4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 12, 2023 | The GPC4 c.1469G>A variant is predicted to result in the amino acid substitution p.Ser490Asn. This variant is located in the first nucleotide of exon 9 and is predicted to weaken the splice acceptor site (Alamut Visual Plus v1.6.1). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at