12-62302818-C-T

Variant names:

• chr12-62302818-C-T
• rs11174420
• NM_001252078.2:c.246C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6 BP7 BA1

The NM_001252078.2(USP15):​c.246C>T​(p.His82His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,610,132 control chromosomes in the GnomAD database, including 77,114 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.33 (8904 hom., cov: 32)
  • Exomes 𝑓: 0.30 (68210 hom.)
• Consequence: USP15 NM_001252078.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.28
• Publications: 17 publications found

Genes affected

USP15 (HGNC:12613): (ubiquitin specific peptidase 15) This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-62302818-C-T is Benign according to our data. Variant chr12-62302818-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060061.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252078.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP15	NM_001252078.2	MANE Select	c.246C>T	p.His82His	synonymous	Exon 3 of 22	NP_001239007.1	Q9Y4E8-1
	USP15	NM_006313.3		c.246C>T	p.His82His	synonymous	Exon 3 of 21	NP_006304.1	Q9Y4E8-2
	USP15	NM_001252079.2		c.246C>T	p.His82His	synonymous	Exon 3 of 7	NP_001239008.1	Q9Y4E8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP15	ENST00000280377.10	TSL:1 MANE Select	c.246C>T	p.His82His	synonymous	Exon 3 of 22	ENSP00000280377.5	Q9Y4E8-1
	USP15	ENST00000353364.7	TSL:1	c.246C>T	p.His82His	synonymous	Exon 3 of 21	ENSP00000258123.4	Q9Y4E8-2
	USP15	ENST00000312635.10	TSL:1	c.246C>T	p.His82His	synonymous	Exon 3 of 7	ENSP00000309240.6	Q9Y4E8-4

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50365 AN: 151808 Hom.: 8898 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.280 AC: 70007 AN: 250460 AF XY: 0.282

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.302 AC: 439880 AN: 1458206 Hom.: 68210 Cov.: 33 AF XY: 0.301 AC XY: 218693 AN XY: 725440

African (AFR) AF: 0.463 AC: 15464 AN: 33380

American (AMR) AF: 0.204 AC: 9095 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6235 AN: 26026

East Asian (EAS) AF: 0.162 AC: 6417 AN: 39626

South Asian (SAS) AF: 0.302 AC: 25937 AN: 85880

European-Finnish (FIN) AF: 0.245 AC: 13076 AN: 53304

Middle Eastern (MID) AF: 0.326 AC: 1874 AN: 5744

European-Non Finnish (NFE) AF: 0.310 AC: 343643 AN: 1109436

Other (OTH) AF: 0.301 AC: 18139 AN: 60186

GnomAD4 genome AF: 0.332 AC: 50386 AN: 151926 Hom.: 8904 Cov.: 32 AF XY: 0.326 AC XY: 24190 AN XY: 74242

African (AFR) AF: 0.460 AC: 19064 AN: 41424

American (AMR) AF: 0.267 AC: 4063 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3464

East Asian (EAS) AF: 0.145 AC: 749 AN: 5174

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2497 AN: 10532

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20608 AN: 67954

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.315 Hom.: 25531

Bravo AF: 0.338

Asia WGS AF: 0.224 AC: 782 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	USP15-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.2
DANN	Benign	0.56
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs11174420; hg19: chr12-62696599; COSMIC: COSV54792251; COSMIC: COSV54792251;