10-86668410-G-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001368064.1(LDB3):c.-23-259G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 522,536 control chromosomes in the GnomAD database, including 19,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.29 ( 7269 hom., cov: 34)
Exomes 𝑓: 0.24 ( 11733 hom. )
Consequence
LDB3
NM_001368064.1 intron
NM_001368064.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0320
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 10-86668410-G-T is Benign according to our data. Variant chr10-86668410-G-T is described in ClinVar as [Benign]. Clinvar id is 671243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_001368063.1 | c.-23-259G>T | intron_variant | ||||
LDB3 | NM_001368064.1 | c.-23-259G>T | intron_variant | ||||
LDB3 | NM_001368068.1 | c.-23-259G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000688001.1 | c.-23-259G>T | intron_variant | A2 | |||||
LDB3 | ENST00000688785.1 | c.-23-259G>T | intron_variant | ||||||
LDB3 | ENST00000691462.1 | c.-23-259G>T | intron_variant | ||||||
LDB3 | ENST00000687856.1 | c.-23-259G>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.287 AC: 43712AN: 152120Hom.: 7262 Cov.: 34
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GnomAD4 exome AF: 0.237 AC: 87915AN: 370298Hom.: 11733 Cov.: 0 AF XY: 0.235 AC XY: 46044AN XY: 195544
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GnomAD4 genome AF: 0.287 AC: 43751AN: 152238Hom.: 7269 Cov.: 34 AF XY: 0.291 AC XY: 21633AN XY: 74424
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at