rs684232

Variant names:

• chr17-715725-T-C
• rs684232
• ENST00000680704.1:c.-282-5112A>G

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS53	ENST00000680704.1	c.-282-5112A>G		intron_variant	Intron 1 of 18			ENSP00000506453.1

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;