chr12-122232410-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_022916.6(VPS33A):c.1627C>T(p.Arg543Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,394 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_022916.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS33A | NM_022916.6 | c.1627C>T | p.Arg543Ter | stop_gained | 13/13 | ENST00000267199.9 | |
VPS33A | NM_001351018.2 | c.1594C>T | p.Arg532Ter | stop_gained | 13/13 | ||
VPS33A | NM_001351019.2 | c.1579C>T | p.Arg527Ter | stop_gained | 13/13 | ||
VPS33A | NM_001351020.2 | c.1306C>T | p.Arg436Ter | stop_gained | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33A | ENST00000267199.9 | c.1627C>T | p.Arg543Ter | stop_gained | 13/13 | 1 | NM_022916.6 | P1 | |
VPS33A | ENST00000643696.1 | c.1750C>T | p.Arg584Ter | stop_gained | 14/14 | ||||
VPS33A | ENST00000543633.5 | c.*1588C>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 5 | ||||
VPS33A | ENST00000544349.6 | c.*1606C>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459394Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725838
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 16, 2021 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with VPS33A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg543*) in the VPS33A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acid(s) of the VPS33A protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.