11-65546811-GCC-GCCC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001130144.3(LTBP3):c.2216dupG(p.Gly740ArgfsTer51) 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LTBP3
NM_001130144.3 frameshift
NM_001130144.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.99
Publications
4 publications found
Genes affected
LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]
LTBP3 Gene-Disease associations (from GenCC):
- brachyolmia-amelogenesis imperfecta syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- geleophysic dysplasia 3Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- Acromicric dysplasiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- geleophysic dysplasiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-65546811-G-GC is Pathogenic according to our data. Variant chr11-65546811-G-GC is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 4081503.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001130144.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LTBP3 | MANE Select | c.2216dupG | p.Gly740ArgfsTer51 | frameshift | Exon 15 of 28 | NP_001123616.1 | Q9NS15-1 | ||
| LTBP3 | c.2216dupG | p.Gly740ArgfsTer51 | frameshift | Exon 15 of 27 | NP_066548.2 | Q9NS15-2 | |||
| LTBP3 | c.1865dupG | p.Gly623ArgfsTer51 | frameshift | Exon 15 of 27 | NP_001157738.1 | Q9NS15 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LTBP3 | TSL:2 MANE Select | c.2216dupG | p.Gly740ArgfsTer51 | frameshift | Exon 15 of 28 | ENSP00000301873.5 | Q9NS15-1 | ||
| LTBP3 | TSL:1 | c.2216dupG | p.Gly740ArgfsTer51 | frameshift | Exon 15 of 27 | ENSP00000326647.4 | Q9NS15-2 | ||
| LTBP3 | TSL:1 | n.*1861dupG | non_coding_transcript_exon | Exon 15 of 27 | ENSP00000432350.1 | E9PRF2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1391350Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 691910
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1391350
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
691910
African (AFR)
AF:
AC:
0
AN:
31608
American (AMR)
AF:
AC:
0
AN:
42722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23792
East Asian (EAS)
AF:
AC:
0
AN:
35036
South Asian (SAS)
AF:
AC:
0
AN:
85736
European-Finnish (FIN)
AF:
AC:
0
AN:
38646
Middle Eastern (MID)
AF:
AC:
0
AN:
5362
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1072458
Other (OTH)
AF:
AC:
0
AN:
55990
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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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