Genetic Variant VPS52:c.*438A>G (chr6-33250403-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022553.6(VPS52):c.*438A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 163,594 control chromosomes in the GnomAD database, including 1,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1274 hom., cov: 32)

Exomes 𝑓: 0.14 ( 144 hom. )

Consequence

VPS52
NM_022553.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

24 publications found

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:

HCG25 (HGNC:20196): (HLA complex group 25)

HCG25 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022553.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS52	NM_022553.6	MANE Select	c.*438A>G	3_prime_UTR	Exon 20 of 20	NP_072047.4
VPS52	NM_001289174.2		c.*438A>G	3_prime_UTR	Exon 19 of 19	NP_001276103.1
VPS52	NM_001289175.1		c.*438A>G	3_prime_UTR	Exon 20 of 20	NP_001276104.1	Q8N1B4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS52	ENST00000445902.3	TSL:1 MANE Select	c.*438A>G	3_prime_UTR	Exon 20 of 20	ENSP00000409952.2	Q8N1B4-1
VPS52	ENST00000865494.1		c.*438A>G	3_prime_UTR	Exon 20 of 20	ENSP00000535553.1
VPS52	ENST00000954722.1		c.*438A>G	3_prime_UTR	Exon 21 of 21	ENSP00000624781.1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18149

AN:

152040

Hom.:

1272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.0813

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0843

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.144

AC:

1649

AN:

11438

Hom.:

144

Cov.:

AF XY:

0.148

AC XY:

857

AN XY:

5794

show subpopulations

African (AFR)

AF:

0.0446

AC:

AN:

426

American (AMR)

AF:

0.112

AC:

AN:

330

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

151

AN:

524

East Asian (EAS)

AF:

0.0678

AC:

AN:

590

South Asian (SAS)

AF:

0.176

AC:

AN:

512

European-Finnish (FIN)

AF:

0.0765

AC:

AN:

366

Middle Eastern (MID)

AF:

0.190

AC:

AN:

European-Non Finnish (NFE)

AF:

0.146

AC:

1159

AN:

7912

Other (OTH)

AF:

0.158

AC:

114

AN:

720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.119

AC:

18161

AN:

152156

Hom.:

1274

Cov.:

AF XY:

0.118

AC XY:

8789

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0582

AC:

2419

AN:

41532

American (AMR)

AF:

0.129

AC:

1971

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

923

AN:

3470

East Asian (EAS)

AF:

0.0811

AC:

420

AN:

5178

South Asian (SAS)

AF:

0.204

AC:

983

AN:

4824

European-Finnish (FIN)

AF:

0.0843

AC:

892

AN:

10586

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10048

AN:

67986

Other (OTH)

AF:

0.161

AC:

340

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

828

1657

2485

3314

4142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

4154

Bravo

AF:

0.119

Asia WGS

AF:

0.175

AC:

607

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.9

(source)

DANN

Benign

0.86

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over