chr17-532865-T-A

Variant names:

• chr17-532865-T-A
• NM_001128159.3:c.2062A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128159.3(VPS53):​c.2062A>T​(p.Ile688Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VPS53 NM_001128159.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90

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]

ENSG00000263300 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS53	NM_001128159.3	c.2062A>T	p.Ile688Phe	missense_variant	Exon 19 of 22	ENST00000437048.7	NP_001121631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS53	ENST00000437048.7	c.2062A>T	p.Ile688Phe	missense_variant	Exon 19 of 22	1	NM_001128159.3	ENSP00000401435.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	.;.;D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.1	M;.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.2	D;D;.;D
REVEL	Benign	0.24
Sift	Uncertain	0.012	D;D;.;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		0.92	P;P;P;D
Vest4		0.87
MutPred		0.49		Gain of catalytic residue at I688 (P = 0.1387);.;Gain of catalytic residue at I688 (P = 0.1387);.;
MVP		0.47
MPC		1.1
ClinPred		0.97	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-436105;