15-90999015-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018668.5(VPS33B):c.1814G>A(p.Ser605Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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 (★). Synonymous variant affecting the same amino acid position (i.e. S605S) has been classified as Likely benign.
Frequency
Consequence
NM_018668.5 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 |
---|---|---|---|---|---|---|---|
VPS33B | NM_018668.5 | c.1814G>A | p.Ser605Asn | missense_variant | 23/23 | ENST00000333371.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33B | ENST00000333371.8 | c.1814G>A | p.Ser605Asn | missense_variant | 23/23 | 1 | NM_018668.5 | P1 | |
VPS33B | ENST00000535906.1 | c.1733G>A | p.Ser578Asn | missense_variant | 22/22 | 2 | |||
VPS33B | ENST00000557470.5 | n.187G>A | non_coding_transcript_exon_variant | 3/3 | 5 | ||||
VPS33B | ENST00000574755.5 | c.*1509G>A | 3_prime_UTR_variant, NMD_transcript_variant | 22/22 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251394Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135876
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461882Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2023 | The c.1814G>A (p.S605N) alteration is located in exon 23 (coding exon 23) of the VPS33B gene. This alteration results from a G to A substitution at nucleotide position 1814, causing the serine (S) at amino acid position 605 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at