10-86716601-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_007078.3(LDB3):c.1506G>A(p.Pro502=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,764 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0085 ( 24 hom., cov: 31)
Exomes 𝑓: 0.00085 ( 17 hom. )
Consequence
LDB3
NM_007078.3 synonymous
NM_007078.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.226
Genes affected
LDB3 (HGNC:15710): (LIM domain binding 3) This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 10-86716601-G-A is Benign according to our data. Variant chr10-86716601-G-A is described in ClinVar as [Benign]. Clinvar id is 45526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86716601-G-A is described in Lovd as [Benign]. Variant chr10-86716601-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.226 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00854 (1297/151926) while in subpopulation AFR AF= 0.0301 (1244/41380). AF 95% confidence interval is 0.0287. There are 24 homozygotes in gnomad4. There are 603 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1297 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1506G>A | p.Pro502= | synonymous_variant | 10/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1506G>A | p.Pro502= | synonymous_variant | 10/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00853 AC: 1295AN: 151808Hom.: 24 Cov.: 31
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GnomAD3 exomes AF: 0.00214 AC: 535AN: 250256Hom.: 14 AF XY: 0.00169 AC XY: 229AN XY: 135376
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GnomAD4 exome AF: 0.000848 AC: 1240AN: 1461838Hom.: 17 Cov.: 36 AF XY: 0.000718 AC XY: 522AN XY: 727216
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GnomAD4 genome AF: 0.00854 AC: 1297AN: 151926Hom.: 24 Cov.: 31 AF XY: 0.00812 AC XY: 603AN XY: 74254
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 23, 2012 | Pro502Pro in exon 12 of LDB3: This variant is not expected to have clinical sign ificance because it has been identified in 2.7% (102/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs45579241). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 06, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 25, 2017 | - - |
Myofibrillar myopathy 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2021 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2015 | 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at