Variant 6-33266677-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000445902.3(VPS52):c.1161C>T(p.Tyr387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,612,514 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0063 ( 50 hom. )

Consequence

VPS52
ENST00000445902.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.585

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=-0.54).

BP6

Variant 6-33266677-G-A is Benign according to our data. Variant chr6-33266677-G-A is described in ClinVar as [Benign]. Clinvar id is 775237.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.585 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS52	NM_022553.6 linkuse as main transcript	c.1161C>T	p.Tyr387=	synonymous_variant	12/20	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.1161C>T	p.Tyr387=	synonymous_variant	12/20	1	NM_022553.6	ENSP00000409952	P1	Q8N1B4-1
VPS52	ENST00000482399.5 linkuse as main transcript	c.*1290C>T		3_prime_UTR_variant	11/19	2		ENSP00000436612
VPS52	ENST00000478934.5 linkuse as main transcript	n.1022C>T		non_coding_transcript_exon_variant	10/18	2
VPS52	ENST00000493379.1 linkuse as main transcript	n.114C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00589

AC:

896

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00754

AC:

1854

AN:

245926

Hom.:

AF XY:

0.00821

AC XY:

1100

AN XY:

134064

show subpopulations

Gnomad AFR exome

AF:

0.00404

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.0126

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.00255

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.00892

GnomAD4 exome

AF:

0.00633

AC:

9239

AN:

1460254

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

4788

AN XY:

726470

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00804

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.00229

Gnomad4 NFE exome

AF:

0.00582

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.00587

AC:

894

AN:

152260

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00647

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00660

Hom.:

Bravo

AF:

0.00637

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00944

EpiControl

AF:

0.00854

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.7

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over