12-62417548-A-C

Variant names:

• chr12-62417548-A-C
• rs10784293
• ENST00000549415.1:c.*346A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549415.1(USP15):​c.*346A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 158,986 control chromosomes in the GnomAD database, including 6,989 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 0.27 (6638 hom., cov: 32)
  • Exomes 𝑓: 0.30 (351 hom.)
• Consequence: USP15 ENST00000549415.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP15	ENST00000549415.1	c.*346A>C		downstream_gene_variant		3		ENSP00000448372.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40445 AN: 151964 Hom.: 6631 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.299 AC: 2067 AN: 6904 Hom.: 351 AF XY: 0.297 AC XY: 1092 AN XY: 3682

African (AFR) AF: 0.0735 AC: 5 AN: 68

American (AMR) AF: 0.300 AC: 245 AN: 816

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 46 AN: 142

East Asian (EAS) AF: 0.417 AC: 180 AN: 432

South Asian (SAS) AF: 0.202 AC: 183 AN: 904

European-Finnish (FIN) AF: 0.454 AC: 99 AN: 218

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.302 AC: 1218 AN: 4036

Other (OTH) AF: 0.316 AC: 91 AN: 288

GnomAD4 genome AF: 0.266 AC: 40452 AN: 152082 Hom.: 6638 Cov.: 32 AF XY: 0.274 AC XY: 20376 AN XY: 74334

African (AFR) AF: 0.0874 AC: 3629 AN: 41544

American (AMR) AF: 0.311 AC: 4752 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1185 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2276 AN: 5164

South Asian (SAS) AF: 0.217 AC: 1047 AN: 4816

European-Finnish (FIN) AF: 0.480 AC: 5066 AN: 10554

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21745 AN: 67958

Other (OTH) AF: 0.248 AC: 523 AN: 2108

Alfa AF: 0.301 Hom.: 3833

Bravo AF: 0.249

Asia WGS AF: 0.300 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.79
PhyloP100		0.035

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10784293; hg19: chr12-62811328;