chr10-86692566-G-T
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4
The NM_007078.3(LDB3):c.891G>T(p.Arg297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,062 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 Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R297K) has been classified as Uncertain significance.
Frequency
Consequence
NM_007078.3 missense
Scores
Clinical Significance
Conservation
Publications
- myofibrillar myopathy 4Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- dilated cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
- familial dilated cardiomyopathyInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000361373.9 | c.891G>T | p.Arg297Ser | missense_variant | Exon 7 of 14 | 1 | NM_007078.3 | ENSP00000355296.3 | ||
LDB3 | ENST00000263066.11 | c.750G>T | p.Arg250Ser | missense_variant | Exon 8 of 9 | 1 | NM_001368067.1 | ENSP00000263066.7 | ||
ENSG00000289258 | ENST00000443292.2 | c.2400G>T | p.Arg800Ser | missense_variant | Exon 17 of 18 | 1 | ENSP00000393132.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251488 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727238 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74344 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Myofibrillar myopathy 4 Uncertain:1
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. This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 250 of the LDB3 protein (p.Arg250Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 464280). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at