rs11632717

Positions:

• chr15-50514383-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005154.5(USP8):​c.*15295T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,214 control chromosomes in the GnomAD database, including 562 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 0.068 (561 hom., cov: 31)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: USP8 NM_005154.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

Genes affected

USP8 (HGNC:12631): (ubiquitin specific peptidase 8) This gene encodes a protein that belongs to the ubiquitin-specific processing protease family of proteins. The encoded protein is thought to regulate the morphology of the endosome by ubiquitination of proteins on this organelle and is involved in cargo sorting and membrane trafficking at the early endosome stage. This protein is required for the cell to enter the S phase of the cell cycle and also functions as a positive regulator in the Hedgehog signaling pathway in development. Pseudogenes of this gene are present on chromosomes 2 and 6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

USP50 (HGNC:20079): (ubiquitin specific peptidase 50) Enables ubiquitin-like protein-specific protease activity. Acts upstream of or within several processes, including nuclear speck organization; positive regulation of NLRP3 inflammasome complex assembly; and positive regulation of macromolecule metabolic process. Predicted to be active in several cellular components, including dendritic spine; midbody; and postsynaptic density. Predicted to be extrinsic component of endosome membrane and extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

USP50 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP8	NM_005154.5	c.*15295T>C		3_prime_UTR_variant	20/20	ENST00000307179.9	NP_005145.3
USP50	NM_203494.5	c.937-13546A>G		intron_variant		ENST00000532404.6	NP_987090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP8	ENST00000307179.9	c.*15295T>C		3_prime_UTR_variant	20/20	1	NM_005154.5	ENSP00000302239.4
USP50	ENST00000532404.6	c.937-13546A>G		intron_variant		5	NM_203494.5	ENSP00000434676.1

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10331 AN: 152082 Hom.: 560 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0702

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 NFE exome AF: 0.214

GnomAD4 genome AF: 0.0680 AC: 10342 AN: 152200 Hom.: 561 Cov.: 31 AF XY: 0.0664 AC XY: 4942 AN XY: 74424

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0502 Hom.: 127

Bravo AF: 0.0742

Asia WGS AF: 0.0390 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.4
DANN	Benign	0.95

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: rs11632717; hg19: chr15-50806580;