3-8733955-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_001234.5(CAV3):c.79C>T(p.Arg27*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CAV3
NM_001234.5 stop_gained
NM_001234.5 stop_gained
Scores
2
3
1
Clinical Significance
Conservation
PhyloP100: 0.525
Publications
2 publications found
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]
SSUH2 (HGNC:24809): (ssu-2 homolog) Involved in odontogenesis. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
SSUH2 Gene-Disease associations (from GenCC):
- dentin dysplasia type IInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 30 pathogenic variants in the truncated region.
PP5
Variant 3-8733955-C-T is Pathogenic according to our data. Variant chr3-8733955-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 846689.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001234.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CAV3 | NM_033337.3 | MANE Select | c.79C>T | p.Arg27* | stop_gained | Exon 1 of 2 | NP_203123.1 | ||
| CAV3 | NM_001234.5 | c.79C>T | p.Arg27* | stop_gained | Exon 1 of 3 | NP_001225.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CAV3 | ENST00000343849.3 | TSL:1 MANE Select | c.79C>T | p.Arg27* | stop_gained | Exon 1 of 2 | ENSP00000341940.2 | ||
| CAV3 | ENST00000397368.2 | TSL:1 | c.79C>T | p.Arg27* | stop_gained | Exon 1 of 3 | ENSP00000380525.2 | ||
| SSUH2 | ENST00000478513.1 | TSL:1 | n.335+8504G>A | intron | N/A |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 151974Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
151974
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460146Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726504 show subpopulations
GnomAD4 exome
AF:
AC:
8
AN:
1460146
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
726504
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33428
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
1
AN:
86200
European-Finnish (FIN)
AF:
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1110482
Other (OTH)
AF:
AC:
0
AN:
60328
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
3
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6
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0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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<30
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Age
GnomAD4 genome 0.00 AC: 0AN: 151974Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74208
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
151974
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74208
African (AFR)
AF:
AC:
0
AN:
41356
American (AMR)
AF:
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5168
South Asian (SAS)
AF:
AC:
0
AN:
4778
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68006
Other (OTH)
AF:
AC:
0
AN:
2092
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Long QT syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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