chr15-90999318-GT-G

Position:

• chr15-90999318-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018668.5(VPS33B):​c.1775-265del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 462,742 control chromosomes in the GnomAD database, including 307 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (196 hom., cov: 29)
  • Exomes 𝑓: 0.088 (111 hom.)
• Consequence: VPS33B NM_018668.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-90999318-GT-G is Benign according to our data. Variant chr15-90999318-GT-G is described in ClinVar as [Benign]. Clinvar id is 1289946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS33B	NM_018668.5	c.1775-265del		intron_variant		ENST00000333371.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS33B	ENST00000333371.8	c.1775-265del		intron_variant		1	NM_018668.5	P1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6419 AN: 146534 Hom.: 199 Cov.: 29

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.00238

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0490

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0543

GnomAD4 exome AF: 0.0883 AC: 27919 AN: 316168 Hom.: 111 Cov.: 0 AF XY: 0.0889 AC XY: 14928 AN XY: 167918

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.0505

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.0949

Gnomad4 FIN exome AF: 0.0729

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0879

GnomAD4 genome AF: 0.0437 AC: 6409 AN: 146574 Hom.: 196 Cov.: 29 AF XY: 0.0418 AC XY: 2982 AN XY: 71260

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.0716

Gnomad4 EAS AF: 0.00239

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.0539

Bravo AF: 0.0409

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs199831273; hg19: chr15-91542548;