10-86668677-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000443292.2(ENSG00000289258):c.1495G>A(p.Ala499Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000709 in 1,608,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
ENSG00000289258
ENST00000443292.2 missense
ENST00000443292.2 missense
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.72
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 10-86668677-G-A is Benign according to our data. Variant chr10-86668677-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 228794.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LDB3 | NM_007078.3 | c.-15G>A | 5_prime_UTR_variant | 2/14 | ENST00000361373.9 | NP_009009.1 | ||
| LDB3 | NM_001368067.1 | c.-15G>A | 5_prime_UTR_variant | 2/9 | ENST00000263066.11 | NP_001354996.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ENSG00000289258 | ENST00000443292.2 | c.1495G>A | p.Ala499Thr | missense_variant | 12/18 | 1 | ENSP00000393132.2 | |||
| LDB3 | ENST00000361373 | c.-15G>A | 5_prime_UTR_variant | 2/14 | 1 | NM_007078.3 | ENSP00000355296.3 | |||
| LDB3 | ENST00000263066 | c.-15G>A | 5_prime_UTR_variant | 2/9 | 1 | NM_001368067.1 | ENSP00000263066.7 |
Frequencies
GnomAD3 genomes 0.000362 AC: 55AN: 152136Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000104 AC: 26AN: 250528Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135746
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GnomAD4 exome AF: 0.0000405 AC: 59AN: 1456420Hom.: 0 Cov.: 31 AF XY: 0.0000304 AC XY: 22AN XY: 724834
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GnomAD4 genome 0.000361 AC: 55AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27AN XY: 74448
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 20, 2015 | Variant classified as Uncertain Significance - Favor Benign. - |
not provided Benign:1
| Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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