rs964453

Variant names:

• chr16-84734629-T-C
• rs964453
• NM_005153.3:c.90+1126T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USP10	NM_005153.3	c.90+1126T>C		intron_variant	Intron 2 of 13	ENST00000219473.12	NP_005144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP10	ENST00000219473.12	c.90+1126T>C		intron_variant	Intron 2 of 13	1	NM_005153.3	ENSP00000219473.7

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

African (AFR) AF: 0.225 AC: 9321 AN: 41510

American (AMR) AF: 0.412 AC: 6296 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 959 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1475 AN: 5178

South Asian (SAS) AF: 0.234 AC: 1130 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2500 AN: 10586

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15641 AN: 68000

Other (OTH) AF: 0.256 AC: 541 AN: 2116

Alfa AF: 0.243 Hom.: 1249

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
PhyloP100		0.013
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: rs964453; hg19: chr16-84768235;