ClinGen Dosage Sensitivity Curation Page

VAMP7

  • Curation Status: Complete

Location Information

  • Xq28 and Yq12
  • GRCh37/hg19 chrX: 155,110,943-155,173,433
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr24: 57,067,838-57,130,289
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Saito et al. (2000) PMID: 10898908 analyzed VAMP7 (aka SYBL1) in 110 patients with bipolar disorder and normal 119 controls and found a trending association of one SNP (G>C transversion in the polypyrimidine tract at the 3' splice acceptor site preceding exon 8) in the male patients compared to controls (p=.06). They did not see this association in females (p =.66). Muller et al. (2002) PMID: 11840509 did a follow-up study in a German population of 164 patients with bipolar disorder and 267 normal controls. They did not find a significant association with the SNP in males, but found a significant association of the homozygous SNP in female probands as compared to controls (p=0.017). Note that the authors mention that this result may be a false positive, since performing a Bonferroni correction results in a p-value of 0.051.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.