rs199739130
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_007078.3(LDB3):โc.764A>Gโ(p.Lys255Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,082 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 (โ โ ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K255E) has been classified as Uncertain significance.
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.764A>G | p.Lys255Arg | missense_variant | 6/14 | ENST00000361373.9 | |
LDB3 | NM_001368067.1 | c.623A>G | p.Lys208Arg | missense_variant | 7/9 | ENST00000263066.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.764A>G | p.Lys255Arg | missense_variant | 6/14 | 1 | NM_007078.3 | P4 | |
LDB3 | ENST00000263066.11 | c.623A>G | p.Lys208Arg | missense_variant | 7/9 | 1 | NM_001368067.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135908
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727222
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 01, 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variantยฌโ is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 191698). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs199739130, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 208 of the LDB3 protein (p.Lys208Arg). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2020 | The p.K255R variant (also known as c.764A>G), located in coding exon 5 of the LDB3 gene, results from an A to G substitution at nucleotide position 764. The lysine at codon 255 is replaced by arginine, an amino acid with highly similar properties. This variant was identified in one individual with dilated cardiomyopathy (Mook OR et al. J. Med. Genet., 2013 Sep;50:614-26). This amino acid position is not 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