1-150067854-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_007259.5(VPS45):c.-4C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,814 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )
Consequence
VPS45
NM_007259.5 5_prime_UTR
NM_007259.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.52
Genes affected
VPS45 (HGNC:14579): (vacuolar protein sorting 45 homolog) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec1 domain family, and shows a high degree of sequence similarity to mouse, rat and yeast Vps45. The exact function of this gene is not known, but its high expression in peripheral blood mononuclear cells suggests a role in trafficking proteins, including inflammatory mediators. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 1-150067854-C-T is Benign according to our data. Variant chr1-150067854-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 991390.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS45 | NM_007259.5 | c.-4C>T | 5_prime_UTR_variant | 1/15 | ENST00000644510.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS45 | ENST00000644510.2 | c.-4C>T | 5_prime_UTR_variant | 1/15 | NM_007259.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152170Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000354 AC: 89AN: 251148Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135764
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GnomAD4 exome AF: 0.000278 AC: 406AN: 1461644Hom.: 0 Cov.: 30 AF XY: 0.000257 AC XY: 187AN XY: 727146
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 24, 2018 | - - |
Congenital neutropenia-myelofibrosis-nephromegaly syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 16, 2020 | - - |
VPS45-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 16, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at