chr2-147938163-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PVS1_StrongPM2BS1_Supporting
The NM_181741.4(ORC4):c.1105A>T(p.Lys369*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000248 in 1,611,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_181741.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250270Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135306
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1459502Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726204
GnomAD4 genome AF: 0.000151 AC: 23AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change creates a premature translational stop signal (p.Lys369*) in the ORC4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acid(s) of the ORC4 protein. This variant is present in population databases (rs372244689, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ORC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1384791). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at