rs769333468
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_018668.5(VPS33B):c.403+2T>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_018668.5 splice_donor
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS33B | NM_018668.5 | c.403+2T>A | splice_donor_variant | ENST00000333371.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33B | ENST00000333371.8 | c.403+2T>A | splice_donor_variant | 1 | NM_018668.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251458Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135900
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727220
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Arthrogryposis, renal dysfunction, and cholestasis 1 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 18, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at