rs116840800

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

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 8.87
Variant links:
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
CAV3NM_033337.3 linkc.189_197delCACCTTCAC p.Thr64_Thr66del disruptive_inframe_deletion 2/2 ENST00000343849.3 NP_203123.1 P56539
CAV3NM_001234.5 linkc.189_197delCACCTTCAC p.Thr64_Thr66del disruptive_inframe_deletion 2/3 NP_001225.1 P56539
OXTRXR_007095681.1 linkn.1885-3003_1885-2995delAAGGTGGTG intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAV3ENST00000343849.3 linkc.189_197delCACCTTCAC p.Thr64_Thr66del disruptive_inframe_deletion 2/21 NM_033337.3 ENSP00000341940.2 P56539
CAV3ENST00000397368.2 linkc.189_197delCACCTTCAC p.Thr64_Thr66del disruptive_inframe_deletion 2/31 ENSP00000380525.2 P56539
CAV3ENST00000472766.1 linkn.155+11610_155+11618delCACCTTCAC intron_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 providedliterature onlyOMIMSep 03, 1999- -
not provided Other:1
not provided, no classification providedcurationLeiden Muscular Dystrophy (CAV3)Apr 15, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199476331; hg19: chr3-8787282; API