rs1701137

Variant names:

• chr17-572682-C-T
• rs1701137
• NM_001128159.3:c.1314-9937G>A

Variant summary

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

The NM_001128159.3(VPS53):​c.1314-9937G>A variant causes a intron change. The variant allele was found at a frequency of 0.496 in 148,094 control chromosomes in the GnomAD database, including 19,533 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 0.50 (19533 hom., cov: 29)
• Consequence: VPS53 NM_001128159.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS53	NM_001128159.3	c.1314-9937G>A		intron_variant	Intron 13 of 21	ENST00000437048.7	NP_001121631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS53	ENST00000437048.7	c.1314-9937G>A		intron_variant	Intron 13 of 21	1	NM_001128159.3	ENSP00000401435.2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 73370 AN: 147996 Hom.: 19517 Cov.: 29

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.496 AC: 73426 AN: 148094 Hom.: 19533 Cov.: 29 AF XY: 0.489 AC XY: 35365 AN XY: 72276

African (AFR) AF: 0.686 AC: 26588 AN: 38732

American (AMR) AF: 0.529 AC: 7919 AN: 14978

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1815 AN: 3454

East Asian (EAS) AF: 0.273 AC: 1407 AN: 5154

South Asian (SAS) AF: 0.510 AC: 2422 AN: 4746

European-Finnish (FIN) AF: 0.313 AC: 3287 AN: 10496

Middle Eastern (MID) AF: 0.617 AC: 179 AN: 290

European-Non Finnish (NFE) AF: 0.421 AC: 28320 AN: 67284

Other (OTH) AF: 0.526 AC: 1081 AN: 2056

Alfa AF: 0.467 Hom.: 2141

Bravo AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.5
DANN	Benign	0.72
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: rs1701137; hg19: chr17-475922;