chr11-19186251-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003476.5(CSRP3):c.379G>A(p.Val127Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,114 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003476.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251366Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135842
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461890Hom.: 1 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727248
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:5
- -
Reported in association with HCM (Walsh et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 31983221, 32880476, 35241752) -
- -
- -
- -
Dilated cardiomyopathy 1M;C2677491:Hypertrophic cardiomyopathy 12 Uncertain:2
- -
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 127 of the CSRP3 protein (p.Val127Ile). This variant is present in population databases (rs149201422, gnomAD 0.02%). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 27532257, 31983221, 32880476). ClinVar contains an entry for this variant (Variation ID: 44697). 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. 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. -
not specified Uncertain:1
The Val127Ile variant in CSRP3 has not been reported in the literature nor previ ously identified by our laboratory. This variant has been identified in 2/4398 A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; dbSNP rs149201422). This frequency is too low to rule out a role in disease. Computational analyses (biochemical a mino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provi de strong support for or against an impact to the protein. In summary, additiona l information is needed to fully assess the clinical significance of the Val127I le variant. -
Cardiovascular phenotype Uncertain:1
The c.379G>A (p.V127I) alteration is located in exon 4 (coding exon 3) of the CSRP3 gene. This alteration results from a G to A substitution at nucleotide position 379, causing the valine (V) at amino acid position 127 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at