NM_014000.3:c.1198G>T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_014000.3(VCL):c.1198G>T(p.Gly400Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,874 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 (★★).
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251398Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135860
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727222
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74258
ClinVar
Submissions by phenotype
not provided Uncertain:3
The p.Gly400Cys variant in VCL has been identified in 1 individual with HCM (LMM data) and 0.02% (6/30616) of South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 166542). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting. -
Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 166542; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function -
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Dilated cardiomyopathy 1W Uncertain:1
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Cardiovascular phenotype Uncertain:1
The p.G400C variant (also known as c.1198G>T), located in coding exon 10 of the VCL gene, results from a G to T substitution at nucleotide position 1198. The glycine at codon 400 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort; however, clinical details are limited (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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