rs461338

Variant names:

• chr6-33250403-T-C
• rs461338
• NM_022553.6:c.*438A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-33250403-T-C
• chr6-33250403-T-G
• chr6-33250403-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 24 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]

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

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.: 0 AF XY: 0.148 AC XY: 857 AN XY: 5794

African (AFR) AF: 0.0446 AC: 19 AN: 426

American (AMR) AF: 0.112 AC: 37 AN: 330

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 151 AN: 524

East Asian (EAS) AF: 0.0678 AC: 40 AN: 590

South Asian (SAS) AF: 0.176 AC: 90 AN: 512

European-Finnish (FIN) AF: 0.0765 AC: 28 AN: 366

Middle Eastern (MID) AF: 0.190 AC: 11 AN: 58

European-Non Finnish (NFE) AF: 0.146 AC: 1159 AN: 7912

Other (OTH) AF: 0.158 AC: 114 AN: 720

GnomAD4 genome AF: 0.119 AC: 18161 AN: 152156 Hom.: 1274 Cov.: 32 AF XY: 0.118 AC XY: 8789 AN XY: 74386

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: 54 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10048 AN: 67986

Other (OTH) AF: 0.161 AC: 340 AN: 2112

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
DANN	Benign	0.86
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs461338; hg19: chr6-33218180;