rs766154973
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_004484.4(GPC3):c.1293-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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 Likely benign (★).
Frequency
Genomes: not found (cov: 20)
Consequence
GPC3
NM_004484.4 splice_region, splice_polypyrimidine_tract, intron
NM_004484.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0008013
2
Clinical Significance
Conservation
PhyloP100: 0.0360
Genes affected
GPC3 (HGNC:4451): (glypican 3) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant X-133661855-A-G is Benign according to our data. Variant chrX-133661855-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 543107.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.1293-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000370818.8 | |||
GPC3 | NM_001164617.2 | c.1362-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
GPC3 | NM_001164618.2 | c.1245-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
GPC3 | NM_001164619.2 | c.1131-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.1293-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 20
GnomAD3 genomes
?
Cov.:
20
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183404Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67868
GnomAD3 exomes
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1
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183404
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1
AN XY:
67868
Gnomad AFR exome
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GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 20
GnomAD4 genome
?
Cov.:
20
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Wilms tumor 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at