8-99391647-C-CAATCATATCAGGCCTCTGA
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_017890.5(VPS13B):c.3027_3045dup(p.Tyr1016IlefsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000341 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q1009Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017890.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.3027_3045dup | p.Tyr1016IlefsTer6 | frameshift_variant | 21/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.3027_3045dup | p.Tyr1016IlefsTer6 | frameshift_variant | 21/62 | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000357162.7 | c.3027_3045dup | p.Tyr1016IlefsTer6 | frameshift_variant | 21/62 | 1 | NM_152564.5 | P1 | |
VPS13B | ENST00000358544.7 | c.3027_3045dup | p.Tyr1016IlefsTer6 | frameshift_variant | 21/62 | 1 | NM_017890.5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251404Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135878
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727234
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74328
ClinVar
Submissions by phenotype
Cohen syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change creates a premature translational stop signal (p.Tyr1016Ilefs*6) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). This variant is present in population databases (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of Cohen syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 370665). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 18, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at