chrX-133692376-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004484.4(GPC3):c.1285G>A(p.Val429Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,210,255 control chromosomes in the GnomAD database, including 24 homozygotes. There are 1,849 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004484.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00350 AC: 396AN: 113168Hom.: 3 Cov.: 24 AF XY: 0.00326 AC XY: 115AN XY: 35304
GnomAD3 exomes AF: 0.00625 AC: 1146AN: 183404Hom.: 11 AF XY: 0.00587 AC XY: 398AN XY: 67854
GnomAD4 exome AF: 0.00469 AC: 5144AN: 1097034Hom.: 21 Cov.: 29 AF XY: 0.00478 AC XY: 1734AN XY: 362442
GnomAD4 genome AF: 0.00351 AC: 397AN: 113221Hom.: 3 Cov.: 24 AF XY: 0.00325 AC XY: 115AN XY: 35367
ClinVar
Submissions by phenotype
not provided Benign:6
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Variant summary: The GPC3 variant, c.1285G>A (p.Val429Met) causes a missense change involving a conserved nucleotide with 2/3 in silico programs (SNPs&GO and MutationTaster not captured here due to low reliability index and p-value, respectively) predict a "benign" outcome, 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 511/87700 (1/171, 188 hemizygotes, 5 homozygotes), 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. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign. -
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not specified Benign:2Other:1
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Simpson-Golabi-Behmel syndrome type 1 Benign:1
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Inborn genetic diseases Benign:1
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. -
Wilms tumor 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at