3-10142092-G-C
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000551.4(VHL):c.245G>C(p.Arg82Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_000551.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.245G>C | p.Arg82Pro | missense_variant | Exon 1 of 3 | ENST00000256474.3 | NP_000542.1 | |
VHL | NM_001354723.2 | c.245G>C | p.Arg82Pro | missense_variant | Exon 1 of 3 | NP_001341652.1 | ||
VHL | NM_198156.3 | c.245G>C | p.Arg82Pro | missense_variant | Exon 1 of 2 | NP_937799.1 | ||
VHL | NR_176335.1 | n.315G>C | non_coding_transcript_exon_variant | Exon 1 of 4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Von Hippel-Lindau syndrome Pathogenic:2
Variant summary: The variant, VHL c.245G>C (p.Arg82Pro) results in a non-conservative amino acid change located in the von Hippel-Lindau disease tumor suppressor, beta/alpha domain and von Hippel-Lindau disease tumor suppressor, beta domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 227066 control chromosomes (gnomAD) and has been reported in the literature in multiple individuals affected with Von Hippel-Lindau Syndrome (Dollfus_2002, Gallou_2004, Chacon-Camacho_2010, Peng_2017). These data indicate that the variant is very likely to be associated with disease. Publications that report experimental evidence evaluating an impact on protein function (Li_2002, German_2016), do not allow convincing conclusions about the variant effect. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. -
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not provided Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at