rs461251

Variant names:

• chr17-715922-A-G
• rs461251
• ENST00000680704.1:c.-282-5309T>C

Variant summary

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

The ENST00000680704.1(VPS53):​c.-282-5309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,808 control chromosomes in the GnomAD database, including 18,923 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 0.48 (18923 hom., cov: 31)
• Consequence: VPS53 ENST00000680704.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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.-282-5309T>C		intron_variant	Intron 1 of 18			ENSP00000506453.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72701 AN: 151690 Hom.: 18888 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.479 AC: 72790 AN: 151808 Hom.: 18923 Cov.: 31 AF XY: 0.477 AC XY: 35401 AN XY: 74178

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.464

Alfa AF: 0.415 Hom.: 8173

Bravo AF: 0.492

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.8
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs461251; hg19: chr17-619162;