rs774886148
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_007078.3(LDB3):āc.550A>Gā(p.Lys184Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.550A>G | p.Lys184Glu | missense_variant | 5/14 | ENST00000361373.9 | |
LDB3 | NM_001368067.1 | c.321+1507A>G | intron_variant | ENST00000263066.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.550A>G | p.Lys184Glu | missense_variant | 5/14 | 1 | NM_007078.3 | P4 | |
LDB3 | ENST00000263066.11 | c.321+1507A>G | intron_variant | 1 | NM_001368067.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000128 AC: 32AN: 249538Hom.: 0 AF XY: 0.0000960 AC XY: 13AN XY: 135414
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1460980Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 726776
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 09, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Stanford Center for Inherited Cardiovascular Disease, Stanford University | Feb 17, 2015 | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. LDB3 p.Lys184Glu Based on the data reviewed below we consider this variant of unknown significance, probably benign. The p.K184E variant (also known as c.550A>G) is located in coding exon 4 of the LDB3 gene. The lysine at codon 184 is replaced by glutamic acid, an amino acid with some similar properties. A journal search did not elucidate any previous reports of this variant in association with disease. In silico analysis with PolyPhen-2 predicts the variant to be benign. The 184 at codon is not well conserved across vertebrate species. In total the variant has not been seen in ~6,500 laboratory controls, published controls and individuals from publicly available population datasets. There is no variation at codon 184 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 7/27/13). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 7/25/13). - |
Dilated cardiomyopathy 1C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 09, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2017 | A variant of uncertain significance has been identified in the LDB3 gene. The K184E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K184E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Though also not observed in these aforementioned populations by the Exome Aggregation Consortium (ExAc), ExAc did observe K184E in 10/11522 (0.09%) alleles from individuals of Latino background. The K184E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. - |
Myofibrillar myopathy 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
LDB3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 16, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at