rs684232

Positions:

• chr17-715725-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680704.1(VPS53):​c.-282-5112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,920 control chromosomes in the GnomAD database, including 17,251 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (17251 hom., cov: 31)
• Consequence: VPS53 ENST00000680704.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

Genes affected

VPS53 (HGNC:25608): (VPS53 subunit of GARP complex) Involved in endocytic recycling and retrograde transport, endosome to Golgi. Acts upstream of or within lysosomal transport. Located in several cellular components, including Golgi apparatus; perinuclear region of cytoplasm; and recycling endosome. Part of EARP complex and GARP complex. Implicated in pontocerebellar hypoplasia type 2E. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS53	ENST00000680704.1	c.-282-5112A>G		intron_variant				ENSP00000506453

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68953 AN: 151802 Hom.: 17216 Cov.: 31

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.454 AC: 69044 AN: 151920 Hom.: 17251 Cov.: 31 AF XY: 0.452 AC XY: 33582 AN XY: 74254

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.449

Alfa AF: 0.373 Hom.: 11535

Bravo AF: 0.468

Asia WGS AF: 0.522 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs684232; hg19: chr17-618965;