rs1554860812
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000361373.9(LDB3):c.1121C>T(p.Ala374Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,298 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A374T) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000361373.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1121C>T | p.Ala374Val | missense_variant | 9/14 | ENST00000361373.9 | NP_009009.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1121C>T | p.Ala374Val | missense_variant | 9/14 | 1 | NM_007078.3 | ENSP00000355296 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460298Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726506
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 21, 2017 | This variant has not been reported in the literature in individuals with a LDB3-related disease. In summary, this variant has uncertain impact on LDB3 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 379 of the LDB3 protein (p.Ala379Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. The LDB3 gene has multiple clinically relevant isoforms. The p.Ala379Val variant occurs in alternate transcript NM_001171610.1, which corresponds to position c.*10566C>T in NM_001080116.1, the primary transcript listed in the Methods. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at