rs964453

Positions:

• chr16-84734629-T-C

Variant summary

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

The NM_005153.3(USP10):​c.90+1126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,174 control chromosomes in the GnomAD database, including 5,089 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 0.25 (5089 hom., cov: 32)
• Consequence: USP10 NM_005153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

Genes affected

USP10 (HGNC:12608): (ubiquitin specific peptidase 10) Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP10	NM_005153.3	c.90+1126T>C		intron_variant		ENST00000219473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP10	ENST00000219473.12	c.90+1126T>C		intron_variant		1	NM_005153.3	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38110 AN: 152056 Hom.: 5090 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.250 AC: 38116 AN: 152174 Hom.: 5089 Cov.: 32 AF XY: 0.255 AC XY: 18984 AN XY: 74404

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.256

Alfa AF: 0.245 Hom.: 1036

Bravo AF: 0.265

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.7
DANN	Benign	0.73

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: rs964453; hg19: chr16-84768235;