rs10519279

Variant names:

• chr15-50539935-G-C
• rs10519279
• NM_203494.5:c.661-1084C>G

Variant summary

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

The NM_203494.5(USP50):​c.661-1084C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,206 control chromosomes in the GnomAD database, including 2,230 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 0.15 (2230 hom., cov: 32)
• Consequence: USP50 NM_203494.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 3 publications found

Genes affected

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP50	NM_203494.5	c.661-1084C>G		intron_variant	Intron 4 of 6	ENST00000532404.6	NP_987090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP50	ENST00000532404.6	c.661-1084C>G		intron_variant	Intron 4 of 6	5	NM_203494.5	ENSP00000434676.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22313 AN: 152088 Hom.: 2231 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.147 AC: 22312 AN: 152206 Hom.: 2230 Cov.: 32 AF XY: 0.147 AC XY: 10927 AN XY: 74422

African (AFR) AF: 0.0399 AC: 1659 AN: 41542

American (AMR) AF: 0.281 AC: 4296 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5184

South Asian (SAS) AF: 0.205 AC: 987 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1382 AN: 10582

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12615 AN: 68014

Other (OTH) AF: 0.185 AC: 390 AN: 2112

Alfa AF: 0.146 Hom.: 246

Bravo AF: 0.154

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.56
PhyloP100		0.57
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: rs10519279; hg19: chr15-50832132;