rs461338

Positions:

• chr6-33250403-T-C

Variant summary

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

The ENST00000445902.3(VPS52):​c.*438A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 163,594 control chromosomes in the GnomAD database, including 1,418 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 0.12 (1274 hom., cov: 32)
  • Exomes 𝑓: 0.14 (144 hom.)
• Consequence: VPS52 ENST00000445902.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

Genes affected

VPS52 (HGNC:10518): (VPS52 subunit of GARP complex) This gene encodes a protein that is similar to the yeast suppressor of actin mutations 2 gene. The yeast protein forms a subunit of the tetrameric Golgi-associated retrograde protein complex that is involved in vesicle trafficking from from both early and late endosomes, back to the trans-Golgi network. This gene is located on chromosome 6 in a head-to-head orientation with the gene encoding ribosomal protein S18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

HCG25 (HGNC:20196): (HLA complex group 25)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS52	NM_022553.6	c.*438A>G		3_prime_UTR_variant	20/20	ENST00000445902.3	NP_072047.4
HCG25	NR_044997.1	n.221-213T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS52	ENST00000445902.3	c.*438A>G		3_prime_UTR_variant	20/20	1	NM_022553.6	ENSP00000409952	P1
HCG25	ENST00000658980.1	n.130-206T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18149 AN: 152040 Hom.: 1272 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.144 AC: 1649 AN: 11438 Hom.: 144 Cov.: 0 AF XY: 0.148 AC XY: 857 AN XY: 5794

Gnomad4 AFR exome AF: 0.0446

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.0678

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.119 AC: 18161 AN: 152156 Hom.: 1274 Cov.: 32 AF XY: 0.118 AC XY: 8789 AN XY: 74386

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.0811

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0843

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.161

Alfa AF: 0.147 Hom.: 2565

Bravo AF: 0.119

Asia WGS AF: 0.175 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.86

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: rs461338; hg19: chr6-33218180;