16-84709272-C-T

Variant names:

• chr16-84709272-C-T
• rs7197843
• NM_005153.3:c.21+9161C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005153.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP10	NM_005153.3	MANE Select	c.21+9161C>T		intron	N/A	NP_005144.2
	USP10	NM_001272075.2		c.33+4412C>T		intron	N/A	NP_001259004.1
	USP10	NR_073577.2		n.112+9161C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP10	ENST00000219473.12	TSL:1 MANE Select	c.21+9161C>T		intron	N/A	ENSP00000219473.7
	USP10	ENST00000540269.6	TSL:1	n.21+9161C>T		intron	N/A	ENSP00000445589.2
	USP10	ENST00000564566.1	TSL:4	n.511C>T		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.714 AC: 10 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.357 AC: 5 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.517 AC: 21438 AN: 41440

American (AMR) AF: 0.359 AC: 5487 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3472

East Asian (EAS) AF: 0.478 AC: 2464 AN: 5154

South Asian (SAS) AF: 0.536 AC: 2577 AN: 4810

European-Finnish (FIN) AF: 0.596 AC: 6283 AN: 10550

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37567 AN: 67954

Other (OTH) AF: 0.501 AC: 1055 AN: 2104

Alfa AF: 0.531 Hom.: 57513

Bravo AF: 0.502

Asia WGS AF: 0.519 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.57
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: rs7197843; hg19: chr16-84742878;