rs774815578
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_007078.3(LDB3):c.2123C>T(p.Pro708Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P708P) has been classified as Likely benign.
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.2123C>T | p.Pro708Leu | missense_variant | 14/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.2123C>T | p.Pro708Leu | missense_variant | 14/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250630Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135504
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461532Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727020
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74370
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*33541C>T in the primary transcript. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 708 of the LDB3 protein (p.Pro708Leu). This variant is present in population databases (rs774815578, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at