NM_017890.5:c.4620delA
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017890.5(VPS13B):c.4620delA(p.Ser1541ProfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T1540T) 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.4620delA | p.Ser1541ProfsTer6 | frameshift_variant | Exon 29 of 62 | ENST00000358544.7 | NP_060360.3 | |
VPS13B | NM_152564.5 | c.4545delA | p.Ser1516ProfsTer6 | frameshift_variant | Exon 29 of 62 | ENST00000357162.7 | NP_689777.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.4620delA | p.Ser1541ProfsTer6 | frameshift_variant | Exon 29 of 62 | 1 | NM_017890.5 | ENSP00000351346.2 | ||
VPS13B | ENST00000357162.7 | c.4545delA | p.Ser1516ProfsTer6 | frameshift_variant | Exon 29 of 62 | 1 | NM_152564.5 | ENSP00000349685.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Short stature;C0575802:Small hand;C0853697:Decreased total neutrophil count;C0854723:Retinal dystrophy;C1839364:Progressive visual loss;C1848673:Short foot;C2937365:Recurrent aphthous stomatitis;C3714756:Intellectual disability;C4551563:Microcephaly Pathogenic:1
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Cohen syndrome Pathogenic:1
This variant was classified as: Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at