chr17-519169-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_001128159.3(VPS53):āc.2458C>Gā(p.Arg820Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,545,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R820R) has been classified as Likely benign.
Frequency
Consequence
NM_001128159.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS53 | NM_001128159.3 | c.2458C>G | p.Arg820Gly | missense_variant | 22/22 | ENST00000437048.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS53 | ENST00000437048.7 | c.2458C>G | p.Arg820Gly | missense_variant | 22/22 | 1 | NM_001128159.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000386 AC: 58AN: 150220Hom.: 0 AF XY: 0.000551 AC XY: 44AN XY: 79886
GnomAD4 exome AF: 0.000156 AC: 217AN: 1393198Hom.: 0 Cov.: 31 AF XY: 0.000237 AC XY: 163AN XY: 687100
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 01, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 04, 2022 | Variant summary: VPS53 c.2458C>G (p.Arg820Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00039 in 150220 control chromosomes, predominantly at a frequency of 0.0026 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in VPS53 causing Pontocerebellar Hypoplasia, Type 2E phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.2458C>G in individuals affected with Pontocerebellar Hypoplasia, Type 2E 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 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at