rs114087868
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_007259.5(VPS45):c.570C>T(p.Cys190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00096 in 1,612,746 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0046 ( 5 hom., cov: 31)
Exomes 𝑓: 0.00058 ( 5 hom. )
Consequence
VPS45
NM_007259.5 synonymous
NM_007259.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.347
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 1-150077225-C-T is Benign according to our data. Variant chr1-150077225-C-T is described in ClinVar as [Benign]. Clinvar id is 541275.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.347 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000582 (850/1460642) while in subpopulation AFR AF= 0.0175 (584/33434). AF 95% confidence interval is 0.0163. There are 5 homozygotes in gnomad4_exome. There are 365 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS45 | NM_007259.5 | c.570C>T | p.Cys190= | synonymous_variant | 6/15 | ENST00000644510.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS45 | ENST00000644510.2 | c.570C>T | p.Cys190= | synonymous_variant | 6/15 | NM_007259.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00460 AC: 699AN: 151986Hom.: 5 Cov.: 31
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GnomAD3 exomes AF: 0.00141 AC: 352AN: 249450Hom.: 2 AF XY: 0.000979 AC XY: 132AN XY: 134834
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GnomAD4 exome AF: 0.000582 AC: 850AN: 1460642Hom.: 5 Cov.: 31 AF XY: 0.000502 AC XY: 365AN XY: 726600
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GnomAD4 genome ? AF: 0.00459 AC: 698AN: 152104Hom.: 5 Cov.: 31 AF XY: 0.00476 AC XY: 354AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital neutropenia-myelofibrosis-nephromegaly syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
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