NM_001368067.1:c.490G>C
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3
The NM_001368067.1(LDB3):c.490G>C(p.Asp164His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D164N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001368067.1 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: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000263066.11 | c.490G>C | p.Asp164His | missense_variant | Exon 6 of 9 | 1 | NM_001368067.1 | ENSP00000263066.7 | ||
LDB3 | ENST00000361373.9 | c.690-4682G>C | intron_variant | Intron 5 of 13 | 1 | NM_007078.3 | ENSP00000355296.3 | |||
ENSG00000289258 | ENST00000443292.2 | c.2199-4682G>C | intron_variant | Intron 15 of 17 | 1 | ENSP00000393132.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249602 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461882Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727242 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368 show subpopulations
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1C;C4721886:Myofibrillar myopathy 4 Uncertain:1
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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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 164 of the LDB3 protein (p.Asp164His). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 532931). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at