rs199507346
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_014000.3(VCL):c.2799G>A(p.Ala933=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,614,126 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A933A) has been classified as Likely benign.
Frequency
Consequence
NM_014000.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.2799G>A | p.Ala933= | synonymous_variant | 19/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.2746-2222G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.2799G>A | p.Ala933= | synonymous_variant | 19/22 | 1 | NM_014000.3 | ||
VCL | ENST00000372755.7 | c.2746-2222G>A | intron_variant | 1 | P1 | ||||
VCL | ENST00000623461.3 | n.5549-2222G>A | intron_variant, non_coding_transcript_variant | 1 | |||||
VCL | ENST00000624354.3 | c.*2554G>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251466Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135914
GnomAD4 exome AF: 0.0000793 AC: 116AN: 1461882Hom.: 0 Cov.: 30 AF XY: 0.0000784 AC XY: 57AN XY: 727240
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74438
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 26, 2015 | p.Ala933Ala in exon 19 of VCL: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 4/66692 European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs199507346). - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Apr 02, 2019 | - - |
Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at