chr12-122232387-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_022916.6(VPS33A):āc.1650T>Cā(p.Leu550=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,558 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000089 ( 0 hom. )
Consequence
VPS33A
NM_022916.6 synonymous
NM_022916.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0370
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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 12-122232387-A-G is Benign according to our data. Variant chr12-122232387-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1534047.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.037 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS33A | NM_022916.6 | c.1650T>C | p.Leu550= | synonymous_variant | 13/13 | ENST00000267199.9 | |
VPS33A | NM_001351018.2 | c.1617T>C | p.Leu539= | synonymous_variant | 13/13 | ||
VPS33A | NM_001351019.2 | c.1602T>C | p.Leu534= | synonymous_variant | 13/13 | ||
VPS33A | NM_001351020.2 | c.1329T>C | p.Leu443= | synonymous_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33A | ENST00000267199.9 | c.1650T>C | p.Leu550= | synonymous_variant | 13/13 | 1 | NM_022916.6 | P1 | |
VPS33A | ENST00000643696.1 | c.1773T>C | p.Leu591= | synonymous_variant | 14/14 | ||||
VPS33A | ENST00000543633.5 | c.*1611T>C | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 5 | ||||
VPS33A | ENST00000544349.6 | c.*1629T>C | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249956Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135226
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461558Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727034
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GnomAD4 genome Cov.: 32
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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 04, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at