6-33267976-CAG-AAC

Variant names:

• chr6-33267976-CAG-AAC
• NM_022553.6:c.820_822delCTGinsGTT
• VPS52 p.Leu274Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_022553.6(VPS52):​c.820_822delCTGinsGTT​(p.Leu274Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: VPS52 NM_022553.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.820_822delCTGinsGTT	p.Leu274Val	missense	N/A	NP_072047.4
	VPS52	NM_001289174.2		c.619_621delCTGinsGTT	p.Leu207Val	missense	N/A	NP_001276103.1
	VPS52	NM_001289175.1		c.445_447delCTGinsGTT	p.Leu149Val	missense	N/A	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.820_822delCTGinsGTT	p.Leu274Val	missense	N/A	ENSP00000409952.2	Q8N1B4-1
	VPS52	ENST00000865494.1		c.901_903delCTGinsGTT	p.Leu301Val	missense	N/A	ENSP00000535553.1
	VPS52	ENST00000954722.1		c.820_822delCTGinsGTT	p.Leu274Val	missense	N/A	ENSP00000624781.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-33235753;