16-70762598-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_018052.5(VAC14):c.1313G>A(p.Arg438Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000867 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. R438W) has been classified as Uncertain significance.
Frequency
Consequence
NM_018052.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251006Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135702
GnomAD4 exome AF: 0.0000883 AC: 129AN: 1461750Hom.: 0 Cov.: 30 AF XY: 0.0000839 AC XY: 61AN XY: 727156
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74340
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1313G>A (p.R438Q) alteration is located in exon 12 (coding exon 12) of the VAC14 gene. This alteration results from a G to A substitution at nucleotide position 1313, causing the arginine (R) at amino acid position 438 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 438 of the VAC14 protein (p.Arg438Gln). This variant is present in population databases (rs199713327, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with VAC14-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at