chr6-33267881-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000445902.3(VPS52):​c.917G>A​(p.Arg306Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,612,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

VPS52
ENST00000445902.3 missense

Scores

2
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.76
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VPS52NM_022553.6 linkuse as main transcriptc.917G>A p.Arg306Gln missense_variant 9/20 ENST00000445902.3 NP_072047.4 Q8N1B4-1B3KMF7Q4VXZ2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VPS52ENST00000445902.3 linkuse as main transcriptc.917G>A p.Arg306Gln missense_variant 9/201 NM_022553.6 ENSP00000409952.2 Q8N1B4-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152162
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
246776
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134446
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000902
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000418
AC:
61
AN:
1460782
Hom.:
0
Cov.:
31
AF XY:
0.0000413
AC XY:
30
AN XY:
726704
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000486
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152162
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000844
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 24, 2023The c.917G>A (p.R306Q) alteration is located in exon 9 (coding exon 9) of the VPS52 gene. This alteration results from a G to A substitution at nucleotide position 917, causing the arginine (R) at amino acid position 306 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Uncertain
0.098
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.0084
T
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.27
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.011
D
Polyphen
1.0
D
Vest4
0.63
MutPred
0.68
Loss of MoRF binding (P = 0.0225);
MVP
0.75
MPC
1.6
ClinPred
0.99
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
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.

Other links and lift over

dbSNP: rs758963410; hg19: chr6-33235658; API