Variant rs213199 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_022553.6(VPS52):c.820C>T(p.Leu274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,612,704 control chromosomes in the GnomAD database, including 115,248 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 0.40 ( 12214 hom., cov: 31)

Exomes 𝑓: 0.37 ( 103034 hom. )

Consequence

VPS52
NM_022553.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

Variant links:

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]

VPS52 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=2.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS52	NM_022553.6 linkuse as main transcript	c.820C>T	p.Leu274=	synonymous_variant	9/20	ENST00000445902.3	NP_072047.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS52	ENST00000445902.3 linkuse as main transcript	c.820C>T	p.Leu274=	synonymous_variant	9/20	1	NM_022553.6	ENSP00000409952	P1	Q8N1B4-1

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60340

AN:

151798

Hom.:

12210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.601

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.389

AC:

95927

AN:

246752

Hom.:

19372

AF XY:

0.388

AC XY:

52167

AN XY:

134444

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.626

Gnomad SAS exome

AF:

0.380

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.371

AC:

542215

AN:

1460788

Hom.:

103034

Cov.:

AF XY:

0.372

AC XY:

270054

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.446

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.646

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.395

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.397

AC:

60362

AN:

151916

Hom.:

12214

Cov.:

AF XY:

0.397

AC XY:

29497

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.601

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.401

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.425

Alfa

AF:

0.372

Hom.:

12519

Bravo

AF:

0.399

Asia WGS

AF:

0.484

AC:

1682

AN:

3478

EpiCase

AF:

0.364

EpiControl

AF:

0.372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.4

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over