chr12-122232650-G-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_022916.6(VPS33A):c.1609+150C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00094 in 1,107,144 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0039 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 3 hom. )
Consequence
VPS33A
NM_022916.6 intron
NM_022916.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.42
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 12-122232650-G-C is Benign according to our data. Variant chr12-122232650-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2430785.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS33A | NM_022916.6 | c.1609+150C>G | intron_variant | ENST00000267199.9 | |||
VPS33A | NM_001351018.2 | c.1576+150C>G | intron_variant | ||||
VPS33A | NM_001351019.2 | c.1561+150C>G | intron_variant | ||||
VPS33A | NM_001351020.2 | c.1288+150C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33A | ENST00000267199.9 | c.1609+150C>G | intron_variant | 1 | NM_022916.6 | P1 | |||
VPS33A | ENST00000643696.1 | c.1732+150C>G | intron_variant | ||||||
VPS33A | ENST00000543633.5 | c.*1570+150C>G | intron_variant, NMD_transcript_variant | 5 | |||||
VPS33A | ENST00000544349.6 | c.*1588+150C>G | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00391 AC: 594AN: 151992Hom.: 5 Cov.: 32
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GnomAD4 exome AF: 0.000469 AC: 448AN: 955034Hom.: 3 AF XY: 0.000394 AC XY: 187AN XY: 475064
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GnomAD4 genome ? AF: 0.00390 AC: 593AN: 152110Hom.: 5 Cov.: 32 AF XY: 0.00377 AC XY: 280AN XY: 74350
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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 | GeneDx | Apr 20, 2019 | See Variant Classification Assertion Criteria. - |
Computational scores
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Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at