rs397517208
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_007078.3(LDB3):c.1317C>T(p.Pro439Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000375 in 1,546,088 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000071 ( 0 hom., cov: 19)
Exomes 𝑓: 0.000041 ( 1 hom. )
Consequence
LDB3
NM_007078.3 synonymous
NM_007078.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.151
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 10-86716412-C-T is Benign according to our data. Variant chr10-86716412-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 45513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.151 with no splicing effect.
BS2
High AC in GnomAdExome4 at 57 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1317C>T | p.Pro439Pro | synonymous_variant | 10/14 | ENST00000361373.9 | NP_009009.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1317C>T | p.Pro439Pro | synonymous_variant | 10/14 | 1 | NM_007078.3 | ENSP00000355296.3 |
Frequencies
GnomAD3 genomes AF: 0.00000709 AC: 1AN: 140998Hom.: 0 Cov.: 19
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GnomAD3 exomes AF: 0.0000871 AC: 15AN: 172176Hom.: 0 AF XY: 0.000130 AC XY: 12AN XY: 92094
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GnomAD4 exome AF: 0.0000406 AC: 57AN: 1405090Hom.: 1 Cov.: 38 AF XY: 0.0000605 AC XY: 42AN XY: 694302
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GnomAD4 genome AF: 0.00000709 AC: 1AN: 140998Hom.: 0 Cov.: 19 AF XY: 0.0000146 AC XY: 1AN XY: 68270
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 23, 2013 | Pro439Pro in exon 12 of LDB3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. Pro439Pro in exon 12 of LDB3 (allele frequenc y = n/a) - |
Myofibrillar myopathy 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 11, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | LDB3: BP4, BP7 - |
LDB3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2019 | 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). - |
Computational scores
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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