1-150093597-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007259.5(VPS45):c.1442G>A(p.Arg481Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R481R) has been classified as Likely benign.
Frequency
Consequence
NM_007259.5 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 |
---|---|---|---|---|---|---|---|
VPS45 | NM_007259.5 | c.1442G>A | p.Arg481Lys | missense_variant | 13/15 | ENST00000644510.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS45 | ENST00000644510.2 | c.1442G>A | p.Arg481Lys | missense_variant | 13/15 | NM_007259.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251374Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135874
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461666Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727138
GnomAD4 genome AF: 0.000125 AC: 19AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74288
ClinVar
Submissions by phenotype
Congenital neutropenia-myelofibrosis-nephromegaly syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 20, 2022 | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 481 of the VPS45 protein (p.Arg481Lys). This variant is present in population databases (rs151292369, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with VPS45-related conditions. ClinVar contains an entry for this variant (Variation ID: 541272). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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