rs763096875
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003476.5(CSRP3):c.352G>A(p.Glu118Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,888 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. E118D) has been classified as Uncertain significance.
Frequency
Consequence
NM_003476.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251354Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135840
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:2
The p.E118K variant (also known as c.352G>A), located in coding exon 3 of the CSRP3 gene, results from a G to A substitution at nucleotide position 352. The glutamic acid at codon 118 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
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Dilated cardiomyopathy 1M;C2677491:Hypertrophic cardiomyopathy 12 Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 118 of the CSRP3 protein (p.Glu118Lys). This variant is present in population databases (rs763096875, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CSRP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 239542). 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 tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at