rs3131597

Variant names:

• chr15-50536798-G-A
• rs3131597
• NM_203494.5:c.803+1911C>T

Variant summary

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

The NM_203494.5(USP50):​c.803+1911C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,720 control chromosomes in the GnomAD database, including 14,876 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 0.44 (14876 hom., cov: 32)
• Consequence: USP50 NM_203494.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP50	NM_203494.5	c.803+1911C>T		intron_variant	Intron 5 of 6	ENST00000532404.6	NP_987090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP50	ENST00000532404.6	c.803+1911C>T		intron_variant	Intron 5 of 6	5	NM_203494.5	ENSP00000434676.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66631 AN: 151602 Hom.: 14874 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.439 AC: 66666 AN: 151720 Hom.: 14876 Cov.: 32 AF XY: 0.444 AC XY: 32875 AN XY: 74118

African (AFR) AF: 0.377 AC: 15586 AN: 41366

American (AMR) AF: 0.545 AC: 8305 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1642 AN: 3456

East Asian (EAS) AF: 0.472 AC: 2433 AN: 5152

South Asian (SAS) AF: 0.435 AC: 2093 AN: 4808

European-Finnish (FIN) AF: 0.421 AC: 4410 AN: 10472

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30534 AN: 67912

Other (OTH) AF: 0.488 AC: 1029 AN: 2110

Alfa AF: 0.432 Hom.: 2281

Bravo AF: 0.447

Asia WGS AF: 0.402 AC: 1399 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.47
DANN	Benign	0.28
PhyloP100		-1.6
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: rs3131597; hg19: chr15-50828995;