rs1556111740
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_004484.4(GPC3):āc.1686G>Cā(p.Leu562=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,204,252 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000091 ( 0 hom., 1 hem., cov: 21)
Exomes š: 0.0000073 ( 0 hom. 2 hem. )
Consequence
GPC3
NM_004484.4 synonymous
NM_004484.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.779
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant X-133536181-C-G is Benign according to our data. Variant chrX-133536181-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 476651.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.779 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.1686G>C | p.Leu562= | synonymous_variant | 8/8 | ENST00000370818.8 | |
GPC3 | NM_001164617.2 | c.1755G>C | p.Leu585= | synonymous_variant | 9/9 | ||
GPC3 | NM_001164618.2 | c.1638G>C | p.Leu546= | synonymous_variant | 8/8 | ||
GPC3 | NM_001164619.2 | c.1524G>C | p.Leu508= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.1686G>C | p.Leu562= | synonymous_variant | 8/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000907 AC: 1AN: 110252Hom.: 0 Cov.: 21 AF XY: 0.0000308 AC XY: 1AN XY: 32460
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GnomAD4 exome AF: 0.00000731 AC: 8AN: 1094000Hom.: 0 Cov.: 30 AF XY: 0.00000556 AC XY: 2AN XY: 359630
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GnomAD4 genome ? AF: 0.00000907 AC: 1AN: 110252Hom.: 0 Cov.: 21 AF XY: 0.0000308 AC XY: 1AN XY: 32460
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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 | Nov 08, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at