rs386834056
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_017890.5(VPS13B):c.10841_10844del(p.Leu3614ProfsTer36) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P3613P) 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 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.10841_10844del | p.Leu3614ProfsTer36 | frameshift_variant | 56/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.10766_10769del | p.Leu3589ProfsTer36 | frameshift_variant | 56/62 | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000357162.7 | c.10766_10769del | p.Leu3589ProfsTer36 | frameshift_variant | 56/62 | 1 | NM_152564.5 | P1 | |
VPS13B | ENST00000358544.7 | c.10841_10844del | p.Leu3614ProfsTer36 | frameshift_variant | 56/62 | 1 | NM_017890.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152066Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251378Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135866
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461742Hom.: 0 AF XY: 0.0000151 AC XY: 11AN XY: 727180
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74270
ClinVar
Submissions by phenotype
Cohen syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at