16-70687939-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_018052.5(VAC14):c.2338G>A(p.Val780Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,556,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_018052.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VAC14 | NM_018052.5 | c.2338G>A | p.Val780Ile | missense_variant | Exon 19 of 19 | ENST00000261776.10 | NP_060522.3 | |
VAC14 | NM_001351157.2 | c.1636G>A | p.Val546Ile | missense_variant | Exon 18 of 18 | NP_001338086.1 | ||
VAC14 | XM_005256038.5 | c.*3924G>A | 3_prime_UTR_variant | Exon 19 of 19 | XP_005256095.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152270Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000460 AC: 10AN: 217574Hom.: 0 AF XY: 0.0000169 AC XY: 2AN XY: 118188
GnomAD4 exome AF: 0.00000285 AC: 4AN: 1404346Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1AN XY: 693778
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152270Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals with VAC14-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant is present in population databases (rs773466199, ExAC 0.1%). This sequence change replaces valine with isoleucine at codon 780 of the VAC14 protein (p.Val780Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at