rs1286042594
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_001130144.3(LTBP3):c.132del(p.Pro45ArgfsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,462,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G44G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001130144.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTBP3 | NM_001130144.3 | c.132del | p.Pro45ArgfsTer25 | frameshift_variant | 1/28 | ENST00000301873.11 | |
LTBP3 | NM_021070.4 | c.132del | p.Pro45ArgfsTer25 | frameshift_variant | 1/27 | ||
LTBP3 | NM_001164266.1 | c.-216del | 5_prime_UTR_variant | 1/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTBP3 | ENST00000301873.11 | c.132del | p.Pro45ArgfsTer25 | frameshift_variant | 1/28 | 2 | NM_001130144.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 150968Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000458 AC: 6AN: 1311052Hom.: 0 Cov.: 31 AF XY: 0.00000619 AC XY: 4AN XY: 646290
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 150968Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73704
ClinVar
Submissions by phenotype
Brachyolmia-amelogenesis imperfecta syndrome Pathogenic:3
Pathogenic, no assertion criteria provided | research | Institute of Human Genetics, University of Ulm | Nov 17, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported to be associated with LTBP3 related disorder (ClinVar ID: VCV000523637, PMID:29625025). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000047, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 11, 2018 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Dec 19, 2019 | - - |
Heritable Thoracic Aortic Disease Other:1
confers sensitivity, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at