rs397516557
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001368067.1(LDB3):c.348C>T(p.Ala116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,968 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
LDB3
NM_001368067.1 synonymous
NM_001368067.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.273
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=-0.37).
BP6
?
Variant 10-86687072-C-T is Benign according to our data. Variant chr10-86687072-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 43877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.273 with no splicing effect.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_001368067.1 | c.348C>T | p.Ala116= | synonymous_variant | 6/9 | ENST00000263066.11 | |
LDB3 | NM_007078.3 | c.690-4824C>T | intron_variant | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000263066.11 | c.348C>T | p.Ala116= | synonymous_variant | 6/9 | 1 | NM_001368067.1 | ||
LDB3 | ENST00000361373.9 | c.690-4824C>T | intron_variant | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000963 AC: 24AN: 249184Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135202
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461684Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 727112
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74460
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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 provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | LDB3: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 23, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 05, 2011 | Ala116Ala in exon 6 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 near a splice junction. - |
Myofibrillar myopathy 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2023 | - - |
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