Variant 6-33266665-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000445902.3(VPS52):c.1173C>T(p.Asp391=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00262 in 1,612,922 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0027 ( 14 hom. )

Consequence

VPS52
ENST00000445902.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-33266665-G-A is Benign according to our data. Variant chr6-33266665-G-A is described in ClinVar as [Benign]. Clinvar id is 770362.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS52	NM_022553.6 linkuse as main transcript	c.1173C>T	p.Asp391=	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.1173C>T	p.Asp391=	synonymous_variant	12/20	1	NM_022553.6	ENSP00000409952	P1	Q8N1B4-1
VPS52	ENST00000482399.5 linkuse as main transcript	c.*1302C>T		3_prime_UTR_variant	11/19	2		ENSP00000436612
VPS52	ENST00000478934.5 linkuse as main transcript	n.1034C>T		non_coding_transcript_exon_variant	10/18	2
VPS52	ENST00000493379.1 linkuse as main transcript	n.126C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00151

AC:

372

AN:

246454

Hom.:

AF XY:

0.00156

AC XY:

210

AN XY:

134322

show subpopulations

Gnomad AFR exome

AF:

0.000596

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00290

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00271

AC:

3959

AN:

1460684

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

1911

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000726

Gnomad4 NFE exome

AF:

0.00328

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00172

AC:

262

AN:

152238

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00167

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00320

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

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.3

DANN

Benign

0.64

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