12-62313805-G-T

Variant names:

• chr12-62313805-G-T
• rs10506440
• NM_001252078.2:c.349-985G>T

Variant summary

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

The NM_001252078.2(USP15):​c.349-985G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,468 control chromosomes in the GnomAD database, including 4,153 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 0.22 (4153 hom., cov: 32)
• Consequence: USP15 NM_001252078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP15	NM_001252078.2	c.349-985G>T		intron_variant	Intron 3 of 21	ENST00000280377.10	NP_001239007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP15	ENST00000280377.10	c.349-985G>T		intron_variant	Intron 3 of 21	1	NM_001252078.2	ENSP00000280377.5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33966 AN: 151350 Hom.: 4155 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 33984 AN: 151468 Hom.: 4153 Cov.: 32 AF XY: 0.221 AC XY: 16327 AN XY: 74016

African (AFR) AF: 0.336 AC: 13915 AN: 41398

American (AMR) AF: 0.150 AC: 2276 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3454

East Asian (EAS) AF: 0.126 AC: 653 AN: 5168

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4814

European-Finnish (FIN) AF: 0.180 AC: 1899 AN: 10550

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13105 AN: 67568

Other (OTH) AF: 0.207 AC: 435 AN: 2102

Alfa AF: 0.111 Hom.: 176

Bravo AF: 0.225

Asia WGS AF: 0.157 AC: 546 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.31
PhyloP100		-0.75
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: rs10506440; hg19: chr12-62707586;