rs3826033

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018668.5(VPS33B):c.1105+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,972 control chromosomes in the GnomAD database, including 21,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1983 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19723 hom. )

Consequence

VPS33B
NM_018668.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.47

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:

ENSG00000284946 (HGNC:):

ENSG00000284946 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-91005371-G-A is Benign according to our data. Variant chr15-91005371-G-A is described in ClinVar as [Benign]. Clinvar id is 261037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-91005371-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS33B	NM_018668.5 link	c.1105+9C>T		intron_variant		ENST00000333371.8	NP_061138.3	Q9H267-1A0A0S2Z577

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS33B	ENST00000333371.8 link	c.1105+9C>T		intron_variant		1	NM_018668.5	ENSP00000327650.4		Q9H267-1
ENSG00000284946	ENST00000643536.1 link	n.1105+9C>T		intron_variant				ENSP00000494429.1		A0A2R8YDQ0

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19625

AN:

151992

Hom.:

1972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.0920

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.187

AC:

47060

AN:

251192

Hom.:

6156

AF XY:

0.183

AC XY:

24801

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.0272

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.0978

Gnomad EAS exome

AF:

0.503

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.147

AC:

214562

AN:

1461862

Hom.:

19723

Cov.:

AF XY:

0.148

AC XY:

107542

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0242

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.100

Gnomad4 EAS exome

AF:

0.488

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.129

AC:

19645

AN:

152110

Hom.:

1983

Cov.:

AF XY:

0.135

AC XY:

10049

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.0920

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.128

Hom.:

2476

Bravo

AF:

0.132

Asia WGS

AF:

0.352

AC:

1220

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Arthrogryposis, renal dysfunction, and cholestasis 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.44

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over