chr3-10149878-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000551.4(VHL):c.555C>A(p.Tyr185*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.555C>A | p.Tyr185* | stop_gained | Exon 3 of 3 | ENST00000256474.3 | NP_000542.1 | |
VHL | NM_198156.3 | c.432C>A | p.Tyr144* | stop_gained | Exon 2 of 2 | NP_937799.1 | ||
VHL | NM_001354723.2 | c.*109C>A | 3_prime_UTR_variant | Exon 3 of 3 | NP_001341652.1 | |||
VHL | NR_176335.1 | n.884C>A | non_coding_transcript_exon_variant | Exon 4 of 4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Von Hippel-Lindau syndrome;C1837915:Chuvash polycythemia Pathogenic:1
This premature translational stop signal has been observed in individual(s) with clinical features of von Hippel-Lindau disease (PMID: 23298237, 33720516). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the VHL protein in which other variant(s) (p.Leu188Val) have been determined to be pathogenic (PMID: 7563486, 7987306, 8772572, 19228690, 23772956). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr185*) in the VHL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the VHL protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.