rs10488538

Variant names:

• chr7-93336472-G-T
• rs10488538
• NM_017667.4:c.2058+2275G>T

Variant summary

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

The NM_017667.4(VPS50):​c.2058+2275G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 152,212 control chromosomes in the GnomAD database, including 69 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 0.024 (69 hom., cov: 32)
• Consequence: VPS50 NM_017667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

VPS50 (HGNC:25956): (VPS50 subunit of EARP/GARPII complex) Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS50	NM_017667.4	c.2058+2275G>T		intron_variant	Intron 22 of 27	ENST00000305866.10	NP_060137.2
VPS50	NM_001257998.2	c.1968+2275G>T		intron_variant	Intron 23 of 28		NP_001244927.1
VPS50	XM_011516395.3	c.1491+2275G>T		intron_variant	Intron 21 of 26		XP_011514697.1
VPS50	XM_024446826.2	c.1251+2275G>T		intron_variant	Intron 14 of 19		XP_024302594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS50	ENST00000305866.10	c.2058+2275G>T		intron_variant	Intron 22 of 27	1	NM_017667.4	ENSP00000307666.5

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3686 AN: 152094 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.00802

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0224

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

GnomAD4 genome AF: 0.0242 AC: 3687 AN: 152212 Hom.: 69 Cov.: 32 AF XY: 0.0245 AC XY: 1824 AN XY: 74424

Gnomad4 AFR AF: 0.0447 AC: 0.0447301 AN: 0.0447301

Gnomad4 AMR AF: 0.0148 AC: 0.0147867 AN: 0.0147867

Gnomad4 ASJ AF: 0.0228 AC: 0.0227535 AN: 0.0227535

Gnomad4 EAS AF: 0.0883 AC: 0.088258 AN: 0.088258

Gnomad4 SAS AF: 0.0413 AC: 0.0412863 AN: 0.0412863

Gnomad4 FIN AF: 0.00802 AC: 0.0080219 AN: 0.0080219

Gnomad4 NFE AF: 0.0108 AC: 0.0107644 AN: 0.0107644

Gnomad4 OTH AF: 0.0232 AC: 0.0231569 AN: 0.0231569

Alfa AF: 0.0155 Hom.: 8

Bravo AF: 0.0251

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.68
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

Publications

LitVar

Other links and lift over

dbSNP: rs10488538; hg19: chr7-92965784;