chr12-122232446-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_022916.6(VPS33A):c.1610-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,601,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
VPS33A
NM_022916.6 intron
NM_022916.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.78
Genes affected
VPS33A (HGNC:18179): (VPS33A core subunit of CORVET and HOPS complexes) This gene encodes a tethering protein and a core subunit of the homotypic fusion and protein sorting (HOPS) complex. The HOPS complex and a second endosomal tethering complex called the class C core vacuole/endosome tethering (CORVET) complex, perform diverse functions in endocytosis including membrane tethering, RabGTPase interaction, activation and proofreading of synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) assembly to drive membrane fusion, and endosome-to-cytoskeleton attachment. The HOPS complex controls endosome maturation as well as endosome traffic to the lysosome. This complex is essential for vacuolar fusion and is required for adaptor protein complex 3-dependent transport from the golgi to the vacuole. The encoded protein belongs to the Sec1/Munc18 (SM) family of SNARE-mediated membrane fusion regulators. Naturally occurring mutations in this gene are associated with a novel mucopolysaccharidosis-like disease. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 12-122232446-A-C is Benign according to our data. Variant chr12-122232446-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1666156.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS33A | NM_022916.6 | c.1610-19T>G | intron_variant | ENST00000267199.9 | |||
VPS33A | NM_001351018.2 | c.1577-19T>G | intron_variant | ||||
VPS33A | NM_001351019.2 | c.1562-19T>G | intron_variant | ||||
VPS33A | NM_001351020.2 | c.1289-19T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33A | ENST00000267199.9 | c.1610-19T>G | intron_variant | 1 | NM_022916.6 | P1 | |||
VPS33A | ENST00000643696.1 | c.1733-19T>G | intron_variant | ||||||
VPS33A | ENST00000543633.5 | c.*1571-19T>G | intron_variant, NMD_transcript_variant | 5 | |||||
VPS33A | ENST00000544349.6 | c.*1589-19T>G | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152252Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000426 AC: 1AN: 234522Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 127640
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GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449522Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 720876
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74382
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at