chr14-96856542-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_003384.3(VRK1):āc.845T>Cā(p.Ile282Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,514 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. I282I) has been classified as Likely benign.
Frequency
Consequence
NM_003384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VRK1 | NM_003384.3 | c.845T>C | p.Ile282Thr | missense_variant | 10/13 | ENST00000216639.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VRK1 | ENST00000216639.8 | c.845T>C | p.Ile282Thr | missense_variant | 10/13 | 1 | NM_003384.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250764Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135600
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461312Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726996
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74354
ClinVar
Submissions by phenotype
Pontocerebellar hypoplasia type 1A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 21, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 282 of the VRK1 protein (p.Ile282Thr). This variant is present in population databases (rs371024271, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with VRK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 578869). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2022 | The p.I282T variant (also known as c.845T>C), located in coding exon 9 of the VRK1 gene, results from a T to C substitution at nucleotide position 845. The isoleucine at codon 282 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. 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