rs116840800
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM4PP3PP5
The NM_033337.3(CAV3):c.189_197delCACCTTCAC(p.Thr64_Thr66del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CAV3
NM_033337.3 disruptive_inframe_deletion
NM_033337.3 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.87
Genes affected
CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]
OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a topological_domain Cytoplasmic (size 82) in uniprot entity CAV3_HUMAN there are 46 pathogenic changes around while only 9 benign (84%) in NM_033337.3
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_033337.3.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 3-8745596-ACACCACCTT-A is Pathogenic according to our data. Variant chr3-8745596-ACACCACCTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 8277.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-8745596-ACACCACCTT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAV3 | NM_033337.3 | c.189_197delCACCTTCAC | p.Thr64_Thr66del | disruptive_inframe_deletion | 2/2 | ENST00000343849.3 | NP_203123.1 | |
CAV3 | NM_001234.5 | c.189_197delCACCTTCAC | p.Thr64_Thr66del | disruptive_inframe_deletion | 2/3 | NP_001225.1 | ||
OXTR | XR_007095681.1 | n.1885-3003_1885-2995delAAGGTGGTG | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAV3 | ENST00000343849.3 | c.189_197delCACCTTCAC | p.Thr64_Thr66del | disruptive_inframe_deletion | 2/2 | 1 | NM_033337.3 | ENSP00000341940.2 | ||
CAV3 | ENST00000397368.2 | c.189_197delCACCTTCAC | p.Thr64_Thr66del | disruptive_inframe_deletion | 2/3 | 1 | ENSP00000380525.2 | |||
CAV3 | ENST00000472766.1 | n.155+11610_155+11618delCACCTTCAC | intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Rippling muscle disease 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 03, 1999 | - - |
not provided Other:1
not provided, no classification provided | curation | Leiden Muscular Dystrophy (CAV3) | Apr 15, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at