rs1555112641
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_014000.3(VCL):c.166C>T(p.Arg56Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000508 in 1,377,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. R56Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_014000.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.166C>T | p.Arg56Trp | missense_variant, splice_region_variant | 1/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.166C>T | p.Arg56Trp | missense_variant, splice_region_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.166C>T | p.Arg56Trp | missense_variant, splice_region_variant | 1/22 | 1 | NM_014000.3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000508 AC: 7AN: 1377626Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 2AN XY: 678336
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2017 | This sequence change replaces arginine with tryptophan at codon 56 of the VCL protein (p.Arg56Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. While this variant is not present in population databases (no rsID), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a VCL-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. 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