rs745866775
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017890.5(VPS13B):c.10738G>A(p.Val3580Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V3580A) has been classified as Uncertain significance.
Frequency
Consequence
NM_017890.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.10738G>A | p.Val3580Met | missense_variant | 56/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.10663G>A | p.Val3555Met | missense_variant | 56/62 | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.10738G>A | p.Val3580Met | missense_variant | 56/62 | 1 | NM_017890.5 | ||
VPS13B | ENST00000357162.7 | c.10663G>A | p.Val3555Met | missense_variant | 56/62 | 1 | NM_152564.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251366Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135854
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461690Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727112
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Cohen syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 3580 of the VPS13B protein (p.Val3580Met). This variant is present in population databases (rs745866775, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 212569). 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 17, 2014 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2023 | The c.10738G>A (p.V3580M) alteration is located in exon 56 (coding exon 55) of the VPS13B gene. This alteration results from a G to A substitution at nucleotide position 10738, causing the valine (V) at amino acid position 3580 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at