rs2955626

Variant names:

• chr17-714860-C-A
• rs2955626
• ENST00000679865.1:c.-151G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-714860-C-A
• chr17-714860-C-G
• chr17-714860-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000679865.1(VPS53):​c.-151G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 644,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: VPS53 ENST00000679865.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 0 publications found

Genes affected

VPS53 (HGNC:25608): (VPS53 subunit of GARP complex) Involved in endocytic recycling and retrograde transport, endosome to Golgi. Acts upstream of or within lysosomal transport. Located in several cellular components, including Golgi apparatus; perinuclear region of cytoplasm; and recycling endosome. Part of EARP complex and GARP complex. Implicated in pontocerebellar hypoplasia type 2E. [provided by Alliance of Genome Resources, Apr 2022]

VPS53 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2E

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• pontocerebellar hypoplasia, type 13

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• progressive cerebello-cerebral atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS53	NM_001128159.3	c.-151G>T		upstream_gene_variant		ENST00000437048.7	NP_001121631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS53	ENST00000437048.7	c.-151G>T		upstream_gene_variant		1	NM_001128159.3	ENSP00000401435.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000310 AC: 2 AN: 644470 Hom.: 0 Cov.: 8 AF XY: 0.00000293 AC XY: 1 AN XY: 340834

African (AFR) AF: 0.00 AC: 0 AN: 17246

American (AMR) AF: 0.00 AC: 0 AN: 31076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17076

East Asian (EAS) AF: 0.00 AC: 0 AN: 33008

South Asian (SAS) AF: 0.0000165 AC: 1 AN: 60530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2744

European-Non Finnish (NFE) AF: 0.00000241 AC: 1 AN: 414386

Other (OTH) AF: 0.00 AC: 0 AN: 33018

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		-0.21
PromoterAI		-0.026	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2955626; hg19: chr17-618100;