rs1556233454
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_004484.4(GPC3):āc.1409A>Gā(p.Asn470Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N470K) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 19)
Exomes š: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
GPC3
NM_004484.4 missense
NM_004484.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 4.70
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 -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.40235856).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.1409A>G | p.Asn470Ser | missense_variant | 6/8 | ENST00000370818.8 | |
GPC3 | NM_001164617.2 | c.1478A>G | p.Asn493Ser | missense_variant | 7/9 | ||
GPC3 | NM_001164618.2 | c.1361A>G | p.Asn454Ser | missense_variant | 6/8 | ||
GPC3 | NM_001164619.2 | c.1247A>G | p.Asn416Ser | missense_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.1409A>G | p.Asn470Ser | missense_variant | 6/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 19
GnomAD3 genomes
?
Cov.:
19
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1039029Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 317601
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1039029
Hom.:
Cov.:
24
AF XY:
AC XY:
0
AN XY:
317601
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 19
GnomAD4 genome
?
Cov.:
19
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GPC3-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 470 of the GPC3 protein (p.Asn470Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Uncertain
T;T;T
Polyphen
D;.;.
Vest4
MutPred
Gain of disorder (P = 0.0748);.;.;
MVP
MPC
0.31
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at