rs10521109

Variant names:

• chr17-710261-A-C
• rs10521109
• NM_001128159.3:c.168+272T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-710261-A-C
• chr17-710261-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001128159.3(VPS53):​c.168+272T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,160 control chromosomes in the GnomAD database, including 1,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1936 hom., cov: 32)
• Consequence: VPS53 NM_001128159.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-710261-A-C is Benign according to our data. Variant chr17-710261-A-C is described in ClinVar as Benign. ClinVar VariationId is 671930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS53	NM_001128159.3	c.168+272T>G		intron_variant	Intron 2 of 21	ENST00000437048.7	NP_001121631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS53	ENST00000437048.7	c.168+272T>G		intron_variant	Intron 2 of 21	1	NM_001128159.3	ENSP00000401435.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23356 AN: 152042 Hom.: 1928 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.154 AC: 23387 AN: 152160 Hom.: 1936 Cov.: 32 AF XY: 0.155 AC XY: 11538 AN XY: 74396

African (AFR) AF: 0.109 AC: 4509 AN: 41518

American (AMR) AF: 0.207 AC: 3163 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3468

East Asian (EAS) AF: 0.189 AC: 979 AN: 5180

South Asian (SAS) AF: 0.233 AC: 1123 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1641 AN: 10588

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11058 AN: 67988

Other (OTH) AF: 0.179 AC: 379 AN: 2116

Alfa AF: 0.161 Hom.: 1046

Bravo AF: 0.153

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		2.4
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: rs10521109; hg19: chr17-613501;