chr11-65539085-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001130144.3(LTBP3):c.3907C>A(p.Arg1303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,253,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1303H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130144.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTBP3 | NM_001130144.3 | c.3907C>A | p.Arg1303Ser | missense_variant | 28/28 | ENST00000301873.11 | |
LTBP3 | NM_021070.4 | c.3766C>A | p.Arg1256Ser | missense_variant | 27/27 | ||
LTBP3 | NM_001164266.1 | c.3415C>A | p.Arg1139Ser | missense_variant | 27/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTBP3 | ENST00000301873.11 | c.3907C>A | p.Arg1303Ser | missense_variant | 28/28 | 2 | NM_001130144.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 7.98e-7 AC: 1AN: 1253072Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1AN XY: 612142
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Brachyolmia-amelogenesis imperfecta syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1303 of the LTBP3 protein (p.Arg1303Ser). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The p.R1303S variant (also known as c.3907C>A), located in coding exon 28 of the LTBP3 gene, results from a C to A substitution at nucleotide position 3907. The arginine at codon 1303 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at