rs870181

chr17-697017-C-T

Variant summary

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

The NM_001128159.3(VPS53):c.285+401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,048 control chromosomes in the GnomAD database, including 4,016 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 0.22 (4016 hom., cov: 31)
• Consequence: VPS53 NM_001128159.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS53	NM_001128159.3	c.285+401G>A		intron_variant		ENST00000437048.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS53	ENST00000437048.7	c.285+401G>A		intron_variant		1	NM_001128159.3	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33664 AN: 151932 Hom.: 4019 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.221 AC: 33645 AN: 152048 Hom.: 4016 Cov.: 31 AF XY: 0.217 AC XY: 16151 AN XY: 74318

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.0949

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.224

Alfa AF: 0.259 Hom.: 2856

Bravo AF: 0.220

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.9
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs870181; hg19: chr17-600257;