rs78696048
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_004484.4(GPC3):āc.995A>Gā(p.Gln332Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,208,817 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_004484.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC3 | NM_004484.4 | c.995A>G | p.Gln332Arg | missense_variant | 3/8 | ENST00000370818.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC3 | ENST00000370818.8 | c.995A>G | p.Gln332Arg | missense_variant | 3/8 | 1 | NM_004484.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000634 AC: 71AN: 111933Hom.: 0 Cov.: 22 AF XY: 0.000645 AC XY: 22AN XY: 34103
GnomAD3 exomes AF: 0.000164 AC: 30AN: 183278Hom.: 0 AF XY: 0.000118 AC XY: 8AN XY: 67766
GnomAD4 exome AF: 0.0000675 AC: 74AN: 1096829Hom.: 0 Cov.: 32 AF XY: 0.0000552 AC XY: 20AN XY: 362215
GnomAD4 genome ? AF: 0.000634 AC: 71AN: 111988Hom.: 0 Cov.: 22 AF XY: 0.000644 AC XY: 22AN XY: 34168
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 19, 2018 | Variant summary: GPC3 c.995A>G (p.Gln332Arg) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00021 in 200296 control chromosomes, predominantly at a frequency of 0.0023 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately significantly higher than the estimated maximal expected allele frequency for a pathogenic variant in GPC3 causing Wilms Tumor, Type 1 phenotype (6.3e-08), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.995A>G in individuals affected with Wilms Tumor, Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2020 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2020 | - - |
Wilms tumor 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at