rs397516556
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2
The NM_001368067.1(LDB3):c.324G>A(p.Val108=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V108V) has been classified as Likely benign.
Frequency
Consequence
NM_001368067.1 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_001368067.1 | c.324G>A | p.Val108= | splice_region_variant, synonymous_variant | 5/9 | ENST00000263066.11 | |
LDB3 | NM_007078.3 | c.689+3877G>A | intron_variant | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000263066.11 | c.324G>A | p.Val108= | splice_region_variant, synonymous_variant | 5/9 | 1 | NM_001368067.1 | ||
LDB3 | ENST00000361373.9 | c.689+3877G>A | intron_variant | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249564Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135406
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727220
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 532927). This variant is present in population databases (rs397516556, gnomAD 0.01%). This sequence change affects codon 108 of the LDB3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDB3 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at