Variant rs1555460030 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_018668.5(VPS33B):c.240-577_290-156del variant causes a splice acceptor, splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

VPS33B
NM_018668.5 splice_acceptor, splice_donor, splice_donor_5th_base, coding_sequence, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

VPS33B (HGNC:12712): (VPS33B late endosome and lysosome associated) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec-1 domain family, and encodes the human ortholog of rat Vps33b which is homologous to the yeast class C Vps33 protein. The mammalian class C vacuolar protein sorting proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Mutations in this gene are associated with arthrogryposis-renal dysfunction-cholestasis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

VPS33B links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-91014026-TGGCCAACATGGTGAAACTCTGTCTCTACTAAAAACACAAAAAATTAGCCCGATCTGGTGGTGGGCACCTGTAATCCCAGCTACTTGGGAGGCTAAGGCAAGAGAATCGCTTGAACCCAGGAGGCGGAGGTTGCAGTGAGCCGAGATCGTGCCATTGCACTCCAGACTGGGCAACAAGAGTGAAACTCCGTCTCAAAAAAAAAAAAAAAAAAAAAAAGAAGCGGGGAAGCAGACATCCTCCACAAGTGCTACGGCCAACTCAAACAATTATTTTCTTATTAGAGGGTCCTTATGGCCAAGGCCCTTAGATTTTGCCCGCCCTTTCCCACAGTTACACATAGTACCATGGCACACTCACTGGCAATGTATCGCATATTCTTGATGCGGGGTCTGACCAAGAAGCACAATCTATGAGAGAGAAAGAAAAAAAAACAGTGAAGAAGAATTATCAAGTTGGATAGCAACTTAGAAGAAACTGAAACAATACCAACTCTTTTGCCATTTGCCCTACAGGTCTCATCCTAGCCAAAGCTATGCTATTCTCTTGGTCCACCATATACCAACCACAGAAGATACCTCTCAACACAATGGGTATAATGTGATGAGCTGGGTACATTACTGGCCCTATGGTGGACCCAAAAGTTCCTGTTCTCAAATAATTTACAATCCAGTGGGCAAAAAAAGATGCAGATATGGAGTATATTAACAATCAGTGCTGAAAAACAATATAAGAATACCCCATAAAAATATACAATTATTATCTGTCAGTTAAAAATAAAGGCTGGGCATGGTGGCTCACACCTGTAATCTTAACACTCCGGGAAGCCAAGGTGAGAAGATTGCTTGAGCTCAGGAGTTCGAAACTAGCCTCAGCAACACAGTGAGACCTCATCTCTATTAAAAATAATAATAGTGCTGTAATCCCAGCACTTTGGGAGGCAGAGGCGCGTGGATCACCTGAGGTCAGGAGTTTGAGACCAGCCCA-T is Pathogenic according to our data. Variant chr15-91014026-TGGCCAACATGGTGAAACTCTGTCTCTACTAAAAACACAAAAAATTAGCCCGATCTGGTGGTGGGCACCTGTAATCCCAGCTACTTGGGAGGCTAAGGCAAGAGAATCGCTTGAACCCAGGAGGCGGAGGTTGCAGTGAGCCGAGATCGTGCCATTGCACTCCAGACTGGGCAACAAGAGTGAAACTCCGTCTCAAAAAAAAAAAAAAAAAAAAAAAGAAGCGGGGAAGCAGACATCCTCCACAAGTGCTACGGCCAACTCAAACAATTATTTTCTTATTAGAGGGTCCTTATGGCCAAGGCCCTTAGATTTTGCCCGCCCTTTCCCACAGTTACACATAGTACCATGGCACACTCACTGGCAATGTATCGCATATTCTTGATGCGGGGTCTGACCAAGAAGCACAATCTATGAGAGAGAAAGAAAAAAAAACAGTGAAGAAGAATTATCAAGTTGGATAGCAACTTAGAAGAAACTGAAACAATACCAACTCTTTTGCCATTTGCCCTACAGGTCTCATCCTAGCCAAAGCTATGCTATTCTCTTGGTCCACCATATACCAACCACAGAAGATACCTCTCAACACAATGGGTATAATGTGATGAGCTGGGTACATTACTGGCCCTATGGTGGACCCAAAAGTTCCTGTTCTCAAATAATTTACAATCCAGTGGGCAAAAAAAGATGCAGATATGGAGTATATTAACAATCAGTGCTGAAAAACAATATAAGAATACCCCATAAAAATATACAATTATTATCTGTCAGTTAAAAATAAAGGCTGGGCATGGTGGCTCACACCTGTAATCTTAACACTCCGGGAAGCCAAGGTGAGAAGATTGCTTGAGCTCAGGAGTTCGAAACTAGCCTCAGCAACACAGTGAGACCTCATCTCTATTAAAAATAATAATAGTGCTGTAATCCCAGCACTTTGGGAGGCAGAGGCGCGTGGATCACCTGAGGTCAGGAGTTTGAGACCAGCCCA-T is described in ClinVar as [Pathogenic]. Clinvar id is 88857.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS33B	NM_018668.5 linkuse as main transcript	c.240-577_290-156del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	4/23	ENST00000333371.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS33B	ENST00000333371.8 linkuse as main transcript	c.240-577_290-156del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	4/23	1	NM_018668.5	P1	Q9H267-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Arthrogryposis, renal dysfunction, and cholestasis 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2012

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.