rs201063130
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_007078.3(LDB3):c.1962G>A(p.Glu654=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,124 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
LDB3
NM_007078.3 synonymous
NM_007078.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.38
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 10-86718831-G-A is Benign according to our data. Variant chr10-86718831-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 406803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.38 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 51 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1962G>A | p.Glu654= | synonymous_variant | 12/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1962G>A | p.Glu654= | synonymous_variant | 12/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251260Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135812
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461814Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727208
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1C;C4721886:Myofibrillar myopathy 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 11, 2021 | - - |
Myofibrillar myopathy 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 14, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2019 | This alteration is classified as likely 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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at