rs777709634
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_014000.3(VCL):c.1046C>T(p.Ala349Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A349A) has been classified as Likely benign.
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.1046C>T | p.Ala349Val | missense_variant | 9/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.1046C>T | p.Ala349Val | missense_variant | 9/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.1046C>T | p.Ala349Val | missense_variant | 9/22 | 1 | NM_014000.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251094Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135716
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461786Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727190
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 349 of the VCL protein (p.Ala349Val). This variant is present in population databases (rs777709634, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with VCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 575448). 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. - |
Dilated cardiomyopathy 1W;C2750459:Hypertrophic cardiomyopathy 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 03, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2021 | The p.A349V variant (also known as c.1046C>T), located in coding exon 9 of the VCL gene, results from a C to T substitution at nucleotide position 1046. The alanine at codon 349 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at