rs761905254
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_003384.3(VRK1):c.772C>T(p.His258Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003384.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VRK1 | NM_003384.3 | c.772C>T | p.His258Tyr | missense_variant | 9/13 | ENST00000216639.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VRK1 | ENST00000216639.8 | c.772C>T | p.His258Tyr | missense_variant | 9/13 | 1 | NM_003384.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251258Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135798
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461400Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727048
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Pontocerebellar hypoplasia type 1A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 21, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces histidine with tyrosine at codon 258 of the VRK1 protein (p.His258Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs761905254, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with VRK1-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 tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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