rs200982547
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_017890.5(VPS13B):āc.3297A>Cā(p.Thr1099=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,614,018 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.000051 ( 0 hom. )
Consequence
VPS13B
NM_017890.5 synonymous
NM_017890.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.406
Genes affected
VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 8-99442487-A-C is Benign according to our data. Variant chr8-99442487-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 361056.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.406 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.3297A>C | p.Thr1099= | synonymous_variant | 23/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.3297A>C | p.Thr1099= | synonymous_variant | 23/62 | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.3297A>C | p.Thr1099= | synonymous_variant | 23/62 | 1 | NM_017890.5 | ||
VPS13B | ENST00000357162.7 | c.3297A>C | p.Thr1099= | synonymous_variant | 23/62 | 1 | NM_152564.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000147 AC: 37AN: 251350Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135842
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GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 727176
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74482
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cohen syndrome Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 07, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
VPS13B-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 10, 2019 | 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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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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at