Variant 6-33264910-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022553.6(VPS52):c.1282-10A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,599,286 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 98 hom. )

Consequence

VPS52
NM_022553.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002001

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0140

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 6-33264910-T-A is Benign according to our data. Variant chr6-33264910-T-A is described in ClinVar as [Benign]. Clinvar id is 782824.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1825/152264) while in subpopulation AFR AF= 0.0362 (1504/41528). AF 95% confidence interval is 0.0347. There are 33 homozygotes in gnomad4. There are 869 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS52	NM_022553.6 linkuse as main transcript	c.1282-10A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000445902.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
VPS52	ENST00000445902.3 linkuse as main transcript	c.1282-10A>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_022553.6	P1	Q8N1B4-1
VPS52	ENST00000482399.5 linkuse as main transcript	c.*1411-10A>T	splice_polypyrimidine_tract_variant, intron_variant	2
VPS52	ENST00000478934.5 linkuse as main transcript	n.1143-10A>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
VPS52	ENST00000493379.1 linkuse as main transcript	n.235-10A>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1826

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00673

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00539

AC:

1330

AN:

246722

Hom.:

AF XY:

0.00525

AC XY:

706

AN XY:

134448

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.00351

Gnomad ASJ exome

AF:

0.00271

Gnomad EAS exome

AF:

0.00274

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00625

GnomAD4 exome

AF:

0.00304

AC:

4402

AN:

1447022

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

2214

AN XY:

720710

show subpopulations

Gnomad4 AFR exome

AF:

0.0360

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00269

Gnomad4 EAS exome

AF:

0.00217

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.000172

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.0120

AC:

1825

AN:

152264

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

869

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0362

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00655

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00288

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.0160

AC:

AN:

3478

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

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.8

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.056

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

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