chr6-33267978-G-A

Variant names:

• chr6-33267978-G-A
• rs213199
• NM_022553.6:c.820C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_022553.6(VPS52):​c.820C>T​(p.Leu274Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,612,704 control chromosomes in the GnomAD database, including 115,248 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12214 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103034 hom.)
• Consequence: VPS52 NM_022553.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=2.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS52	NM_022553.6	MANE Select	c.820C>T	p.Leu274Leu	synonymous	Exon 9 of 20	NP_072047.4
	VPS52	NM_001289174.2		c.619C>T	p.Leu207Leu	synonymous	Exon 8 of 19	NP_001276103.1
	VPS52	NM_001289175.1		c.445C>T	p.Leu149Leu	synonymous	Exon 9 of 20	NP_001276104.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS52	ENST00000445902.3	TSL:1 MANE Select	c.820C>T	p.Leu274Leu	synonymous	Exon 9 of 20	ENSP00000409952.2
	VPS52	ENST00000865494.1		c.901C>T	p.Leu301Leu	synonymous	Exon 9 of 20	ENSP00000535553.1
	VPS52	ENST00000954722.1		c.820C>T	p.Leu274Leu	synonymous	Exon 10 of 21	ENSP00000624781.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60340 AN: 151798 Hom.: 12210 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.423

GnomAD2 exomes AF: 0.389 AC: 95927 AN: 246752 AF XY: 0.388

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.626

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.371 AC: 542215 AN: 1460788 Hom.: 103034 Cov.: 66 AF XY: 0.372 AC XY: 270054 AN XY: 726706

African (AFR) AF: 0.446 AC: 14943 AN: 33480

American (AMR) AF: 0.348 AC: 15559 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 11275 AN: 26136

East Asian (EAS) AF: 0.646 AC: 25627 AN: 39700

South Asian (SAS) AF: 0.381 AC: 32902 AN: 86258

European-Finnish (FIN) AF: 0.395 AC: 20663 AN: 52334

Middle Eastern (MID) AF: 0.428 AC: 2470 AN: 5768

European-Non Finnish (NFE) AF: 0.356 AC: 395907 AN: 1112002

Other (OTH) AF: 0.379 AC: 22869 AN: 60386

GnomAD4 genome AF: 0.397 AC: 60362 AN: 151916 Hom.: 12214 Cov.: 31 AF XY: 0.397 AC XY: 29497 AN XY: 74230

African (AFR) AF: 0.431 AC: 17835 AN: 41402

American (AMR) AF: 0.379 AC: 5784 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1478 AN: 3464

East Asian (EAS) AF: 0.601 AC: 3106 AN: 5164

South Asian (SAS) AF: 0.384 AC: 1847 AN: 4814

European-Finnish (FIN) AF: 0.401 AC: 4223 AN: 10534

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24740 AN: 67966

Other (OTH) AF: 0.425 AC: 892 AN: 2100

Alfa AF: 0.376 Hom.: 23674

Bravo AF: 0.399

Asia WGS AF: 0.484 AC: 1682 AN: 3478

EpiCase AF: 0.364

EpiControl AF: 0.372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.4
DANN	Benign	0.83
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs213199; hg19: chr6-33235755; COSMIC: COSV71403493; COSMIC: COSV71403493;