VPS52 p.Leu274Leu

Variant names:

• chr6-33267975-C-C
• NM_022553.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr6-33267976--
• chr6-33267978-G-A
• chr6-33267976-C-A
• chr6-33267976-C-G
• chr6-33267976-C-T
• chr6-33267976-CAG-TAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022553.6(VPS52):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: VPS52 NM_022553.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 9 of 20	NP_072047.4
	VPS52	NM_001289174.2		c.		exon_region	Exon 8 of 19	NP_001276103.1
	VPS52	NM_001289175.1		c.		exon_region	Exon 9 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.		exon_region	Exon 9 of 20	ENSP00000409952.2	Q8N1B4-1
	VPS52	ENST00000865494.1		c.		exon_region	Exon 9 of 20	ENSP00000535553.1
	VPS52	ENST00000954722.1		c.		exon_region	Exon 10 of 21	ENSP00000624781.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

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: chr6-33235752;