6-33266665-G-A

Position:

• chr6-33266665-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022553.6(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 NM_022553.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.79

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]

ACMG classification

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	UniProt
VPS52	NM_022553.6	c.1173C>T	p.Asp391=	synonymous_variant	12/20	ENST00000445902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS52	ENST00000445902.3	c.1173C>T	p.Asp391=	synonymous_variant	12/20	1	NM_022553.6	P1
VPS52	ENST00000482399.5	c.*1302C>T		3_prime_UTR_variant	11/19	2
VPS52	ENST00000478934.5	n.1034C>T		non_coding_transcript_exon_variant	10/18	2
VPS52	ENST00000493379.1	n.126C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 152120 Hom.: 2 Cov.: 31

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.: 1 AF XY: 0.00156 AC XY: 210 AN XY: 134322

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.: 14 Cov.: 31 AF XY: 0.00263 AC XY: 1911 AN XY: 726664

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.: 2 Cov.: 31 AF XY: 0.00144 AC XY: 107 AN XY: 74440

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.: 0

Bravo AF: 0.00167

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00278

EpiControl AF: 0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

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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

Other links and lift over

dbSNP: rs141154095; hg19: chr6-33234442;