rs104893829
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The NM_000551.4(VHL):c.241C>G(p.Pro81Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P81Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000551.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.241C>G | p.Pro81Ala | missense_variant | 1/3 | ENST00000256474.3 | |
VHL | NM_001354723.2 | c.241C>G | p.Pro81Ala | missense_variant | 1/3 | ||
VHL | NM_198156.3 | c.241C>G | p.Pro81Ala | missense_variant | 1/2 | ||
VHL | NR_176335.1 | n.311C>G | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VHL | ENST00000256474.3 | c.241C>G | p.Pro81Ala | missense_variant | 1/3 | 1 | NM_000551.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Von Hippel-Lindau syndrome;C1837915:Chuvash polycythemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 16, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with erythrocytosis (PMID: 24115288). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 81 of the VHL protein (p.Pro81Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.