NM_018668.5:c.1775-267_1775-265dupAAA

Variant names:

• chr15-90999318-G-GTTT
• NM_018668.5:c.1775-267_1775-265dupAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_018668.5(VPS33B):​c.1775-267_1775-265dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS33B NM_018668.5 intron
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000284946 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00017 (57/334342) while in subpopulation EAS AF= 0.00123 (25/20400). AF 95% confidence interval is 0.000851. There are 0 homozygotes in gnomad4_exome. There are 34 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS33B	NM_018668.5	c.1775-267_1775-265dupAAA		intron_variant	Intron 22 of 22	ENST00000333371.8	NP_061138.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS33B	ENST00000333371.8	c.1775-265_1775-264insAAA		intron_variant	Intron 22 of 22	1	NM_018668.5	ENSP00000327650.4
ENSG00000284946	ENST00000643536.1	n.1774+358_1774+359insAAA		intron_variant	Intron 22 of 34			ENSP00000494429.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146634 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000170 AC: 57 AN: 334342 Hom.: 0 Cov.: 0 AF XY: 0.000191 AC XY: 34 AN XY: 177616

Gnomad4 AFR exome AF: 0.000103

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.0000999

Gnomad4 EAS exome AF: 0.00123

Gnomad4 SAS exome AF: 0.0000506

Gnomad4 FIN exome AF: 0.000208

Gnomad4 NFE exome AF: 0.000100

Gnomad4 OTH exome AF: 0.0000520

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146634 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 71256

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-91542548;