16-84709272-C-T

Position:

• chr16-84709272-C-T

Variant summary

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

The NM_005153.3(USP10):​c.21+9161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,984 control chromosomes in the GnomAD database, including 20,937 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 0.52 (20931 hom., cov: 31)
  • Exomes 𝑓: 0.50 (6 hom.)
• Consequence: USP10 NM_005153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

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]

USP10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP10	NM_005153.3	c.21+9161C>T		intron_variant		ENST00000219473.12	NP_005144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP10	ENST00000219473.12	c.21+9161C>T		intron_variant		1	NM_005153.3	ENSP00000219473.7

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79100 AN: 151834 Hom.: 20904 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.500 AC: 15 AN: 30 Hom.: 6 Cov.: 0 AF XY: 0.538 AC XY: 14 AN XY: 26

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.521 AC: 79178 AN: 151954 Hom.: 20931 Cov.: 31 AF XY: 0.519 AC XY: 38559 AN XY: 74252

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.501

Alfa AF: 0.525 Hom.: 21539

Bravo AF: 0.502

Asia WGS AF: 0.519 AC: 1806 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	6.2
DANN	Benign	0.57

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: rs7197843; hg19: chr16-84742878;