11-19182672-ATTCT-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_003476.5(CSRP3):c.579_582delAGAA(p.Lys193AsnfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003476.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSRP3 | NM_003476.5 | c.579_582delAGAA | p.Lys193AsnfsTer14 | frameshift_variant | Exon 6 of 6 | ENST00000265968.9 | NP_003467.1 | |
CSRP3 | NM_001369404.1 | c.410_413delAGAA | p.Lys137MetfsTer19 | frameshift_variant | Exon 5 of 5 | NP_001356333.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461808Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727230
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Lys193fsExtX13 variant in CSRP3 has not been previously reported in indivi duals with cardiomyopathy and data from large population studies is insufficient to assess its frequency. This variant leads to a frameshift at amino acid 193 a nd then alters the stop codon such that 12 additional amino acids are generated before introducing a new stop codon. It is currently unclear how this alteration would impact the protein. In summary, the clinical significance of the p.Lys193 fsExtX13 variant is uncertain. -
Hypertrophic cardiomyopathy Uncertain:1
This sequence change in CSRP3 is a frameshift variant, p.(Lys193Asnfs*14), in biologically relevant exon 6/6 that is predicted to escape nonsense-mediated decay and elongate the protein by 12 amino acids with an unknown effect on protein function. This variant is absent from the population database gnomAD v2.1 and v3.1. To our knowledge, this variant has not been previously reported in the relevant scientific literature. It has been reported as a variant of uncertain significance (ClinVar). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PVS1_Moderate, PM2_Supporting. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at