rs2314298
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004484.4(GPC3):āc.1500T>Cā(p.Asp500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,203,953 control chromosomes in the GnomAD database, including 1,127 homozygotes. There are 4,004 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.062 ( 570 hom., 1822 hem., cov: 22)
Exomes š: 0.0074 ( 557 hom. 2182 hem. )
Consequence
GPC3
NM_004484.4 synonymous
NM_004484.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.89
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant X-133596513-A-G is Benign according to our data. Variant chrX-133596513-A-G is described in ClinVar as [Benign]. Clinvar id is 259405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.88 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.1500T>C | p.Asp500= | synonymous_variant | 7/8 | ENST00000370818.8 | |
GPC3 | NM_001164617.2 | c.1569T>C | p.Asp523= | synonymous_variant | 8/9 | ||
GPC3 | NM_001164618.2 | c.1452T>C | p.Asp484= | synonymous_variant | 7/8 | ||
GPC3 | NM_001164619.2 | c.1338T>C | p.Asp446= | synonymous_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.1500T>C | p.Asp500= | synonymous_variant | 7/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0622 AC: 6938AN: 111568Hom.: 567 Cov.: 22 AF XY: 0.0536 AC XY: 1808AN XY: 33756
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GnomAD3 exomes AF: 0.0192 AC: 3519AN: 183229Hom.: 283 AF XY: 0.0124 AC XY: 838AN XY: 67761
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GnomAD4 exome AF: 0.00741 AC: 8092AN: 1092330Hom.: 557 Cov.: 29 AF XY: 0.00610 AC XY: 2182AN XY: 357832
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GnomAD4 genome ? AF: 0.0624 AC: 6960AN: 111623Hom.: 570 Cov.: 22 AF XY: 0.0539 AC XY: 1822AN XY: 33821
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 05, 2016 | Variant summary: The GPC3 variant, c.1500T>C (p.Asp500Asp) causes a synonymous change involving a non-conserved nucleotide with / in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2082/87736 (1/42, 182 homozygotes, 453 hemizygotes), which significantly exceeds the estimated maximum expected allele frequency for a pathogenic GPC3 variant of 1/10000000. The variant of interest, to our knowledge, has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Simpson-Golabi-Behmel syndrome type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 24, 2020 | - - |
Wilms tumor 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at