12-122232371-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_022916.6(VPS33A):c.1666G>A(p.Ala556Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,032 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 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS33A | NM_022916.6 | c.1666G>A | p.Ala556Thr | missense_variant | Exon 13 of 13 | ENST00000267199.9 | NP_075067.2 | |
VPS33A | NM_001351018.2 | c.1633G>A | p.Ala545Thr | missense_variant | Exon 13 of 13 | NP_001337947.1 | ||
VPS33A | NM_001351019.2 | c.1618G>A | p.Ala540Thr | missense_variant | Exon 13 of 13 | NP_001337948.1 | ||
VPS33A | NM_001351020.2 | c.1345G>A | p.Ala449Thr | missense_variant | Exon 11 of 11 | NP_001337949.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS33A | ENST00000267199.9 | c.1666G>A | p.Ala556Thr | missense_variant | Exon 13 of 13 | 1 | NM_022916.6 | ENSP00000267199.3 | ||
ENSG00000256861 | ENST00000535844.1 | n.1549G>A | non_coding_transcript_exon_variant | Exon 12 of 16 | 2 | ENSP00000454454.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250856Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135670
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727234
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1666G>A (p.A556T) alteration is located in exon 13 (coding exon 13) of the VPS33A gene. This alteration results from a G to A substitution at nucleotide position 1666, causing the alanine (A) at amino acid position 556 to be replaced by a threonine (T). 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