3-10141874-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_000551.4(VHL):c.27C>G(p.Asp9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D9A) has been classified as Likely benign.
Frequency
Consequence
NM_000551.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.27C>G | p.Asp9Glu | missense_variant | 1/3 | ENST00000256474.3 | |
VHL | NM_001354723.2 | c.27C>G | p.Asp9Glu | missense_variant | 1/3 | ||
VHL | NM_198156.3 | c.27C>G | p.Asp9Glu | missense_variant | 1/2 | ||
VHL | NR_176335.1 | n.97C>G | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VHL | ENST00000256474.3 | c.27C>G | p.Asp9Glu | missense_variant | 1/3 | 1 | NM_000551.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Von Hippel-Lindau syndrome;C1837915:Chuvash polycythemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 9 of the VHL protein (p.Asp9Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 846969). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VHL protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at