rs767914340
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_007078.3(LDB3):c.1313C>A(p.Thr438Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,405,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. T438A) has been classified as Likely benign.
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1313C>A | p.Thr438Asn | missense_variant | 10/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1313C>A | p.Thr438Asn | missense_variant | 10/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 133728Hom.: 0 Cov.: 19 FAILED QC
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180850Hom.: 0 AF XY: 0.0000206 AC XY: 2AN XY: 96886
GnomAD4 exome AF: 0.0000107 AC: 15AN: 1405790Hom.: 0 Cov.: 37 AF XY: 0.0000115 AC XY: 8AN XY: 695364
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 133728Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0AN XY: 64246
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 24, 2023 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 438 of the LDB3 protein (p.Thr438Asn). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17034C>A in the primary transcript. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The p.T438N variant (also known as c.1313C>A), located in coding exon 9 of the LDB3 gene, results from a C to A substitution at nucleotide position 1313. The threonine at codon 438 is replaced by asparagine, an amino acid with similar properties. This variant has been detected in an individual reported to have alcohol-induced cardiomyopathy (Ware JS et al. J Am Coll Cardiol. 2018 May;71(20):2293-2302). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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