chr10-86716548-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_007078.3(LDB3):c.1453G>T(p.Ala485Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1453G>T | p.Ala485Ser | missense_variant | 10/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1453G>T | p.Ala485Ser | missense_variant | 10/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000396 AC: 6AN: 151508Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249188Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134888
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461834Hom.: 0 Cov.: 36 AF XY: 0.0000138 AC XY: 10AN XY: 727222
GnomAD4 genome AF: 0.0000396 AC: 6AN: 151626Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74076
ClinVar
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 09, 2014 | The Ala485Ser variant in LDB3 has been identified by our laboratory in 2 Caucasi an adults with DCM and was absent from large population studies. Computational p rediction tools and conservation analysis do not provide strong support for or a gainst an impact to the protein. In summary, the clinical significance of the Va l30899Gly variant is uncertain. - |
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This missense change has been observed in individual(s) with clinical features of LDB3-related conditions (Invitae). This variant is present in population databases (rs397517214, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 485 of the LDB3 protein (p.Ala485Ser). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17174G>T in the primary transcript. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | The c.1453G>T (p.A485S) alteration is located in exon 9 (coding exon 9) of the LDB3 gene. This alteration results from a G to T substitution at nucleotide position 1453, causing the alanine (A) at amino acid position 485 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at