rs760340545
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_014000.3(VCL):c.592G>A(p.Val198Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V198L) has been classified as Uncertain significance.
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.592G>A | p.Val198Met | missense_variant | 5/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.592G>A | p.Val198Met | missense_variant | 5/21 | ||
LOC124902458 | XR_007062200.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.592G>A | p.Val198Met | missense_variant | 5/22 | 1 | NM_014000.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251396Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135868
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461846Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727218
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 14, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Dilated cardiomyopathy 1W;C2750459:Hypertrophic cardiomyopathy 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 16, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at