chr15-50514383-T-C

Variant names:

• chr15-50514383-T-C
• rs11632717
• NM_005154.5:c.*15295T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USP8	NM_005154.5	c.*15295T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000307179.9	NP_005145.3
USP50	NM_203494.5	c.937-13546A>G		intron_variant	Intron 6 of 6	ENST00000532404.6	NP_987090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP8	ENST00000307179.9	c.*15295T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_005154.5	ENSP00000302239.4
USP50	ENST00000532404.6	c.937-13546A>G		intron_variant	Intron 6 of 6	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.214 AC: 3 AN: 14

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.139 AC: 5781 AN: 41492

American (AMR) AF: 0.0569 AC: 870 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5184

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4826

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10620

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0404 AC: 2746 AN: 68006

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0529 Hom.: 212

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
PhyloP100		0.19
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: rs11632717; hg19: chr15-50806580;