rs2955626

Positions:

• chr17-714860-C-G
• chr17-714860-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000679865.1(VPS53):​c.-151G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 795,868 control chromosomes in the GnomAD database, including 123,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (29150 hom., cov: 34)
  • Exomes 𝑓: 0.53 (94543 hom.)
• Consequence: VPS53 ENST00000679865.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-714860-C-G is Benign according to our data. Variant chr17-714860-C-G is described in ClinVar as [Benign]. Clinvar id is 1231609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS53	NM_001128159.3			upstream_gene_variant		ENST00000437048.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS53	ENST00000437048.7			upstream_gene_variant		1	NM_001128159.3	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91267 AN: 152072 Hom.: 29116 Cov.: 34

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.535 AC: 344072 AN: 643678 Hom.: 94543 Cov.: 8 AF XY: 0.531 AC XY: 180778 AN XY: 340418

Gnomad4 AFR exome AF: 0.811

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.843

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.600 AC: 91355 AN: 152190 Hom.: 29150 Cov.: 34 AF XY: 0.602 AC XY: 44783 AN XY: 74418

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.595

Alfa AF: 0.547 Hom.: 2965

Bravo AF: 0.615

Asia WGS AF: 0.667 AC: 2319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2955626; hg19: chr17-618100;