rs397517215
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007078.3(LDB3):c.1471G>A(p.Val491Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V491E) has been classified as Uncertain significance.
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_007078.3 | c.1471G>A | p.Val491Met | missense_variant | 10/14 | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.1471G>A | p.Val491Met | missense_variant | 10/14 | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151742Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249424Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135006
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461846Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727226
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151742Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74058
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2020 | This sequence change replaces valine with methionine at codon 491 of the LDB3 protein (p.Val491Met). The valine residue is highly conserved and there is a small physicochemical difference between the two amino acids. The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17192G>A in the primary transcript. 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 variant has not been reported in the literature in individuals with LDB3-related conditions. This variant is present in population databases (rs397517215, ExAC 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at