12-62384284-A-G

Variant names:

• chr12-62384284-A-G
• rs2044846
• NM_001252078.2:c.1455A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001252078.2(USP15):​c.1455A>G​(p.Pro485Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,605,158 control chromosomes in the GnomAD database, including 300,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (26317 hom., cov: 25)
  • Exomes 𝑓: 0.61 (274501 hom.)
• Consequence: USP15 NM_001252078.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.273
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-62384284-A-G is Benign according to our data. Variant chr12-62384284-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060073.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.273 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 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.1455A>G	p.Pro485Pro	synonymous	Exon 11 of 22	NP_001239007.1	Q9Y4E8-1
	USP15	NM_006313.3		c.1368A>G	p.Pro456Pro	synonymous	Exon 10 of 21	NP_006304.1	Q9Y4E8-2
	USP15	NM_001351159.2		c.1092A>G	p.Pro364Pro	synonymous	Exon 12 of 23	NP_001338088.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP15	ENST00000280377.10	TSL:1 MANE Select	c.1455A>G	p.Pro485Pro	synonymous	Exon 11 of 22	ENSP00000280377.5	Q9Y4E8-1
	USP15	ENST00000353364.7	TSL:1	c.1368A>G	p.Pro456Pro	synonymous	Exon 10 of 21	ENSP00000258123.4	Q9Y4E8-2
	USP15	ENST00000957648.1		c.1578A>G	p.Pro526Pro	synonymous	Exon 12 of 23	ENSP00000627707.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 87854 AN: 147968 Hom.: 26311 Cov.: 25

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.576

GnomAD2 exomes AF: 0.604 AC: 149724 AN: 248070 AF XY: 0.600

Gnomad AFR exome AF: 0.536

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.712

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.613 AC: 892510 AN: 1457116 Hom.: 274501 Cov.: 37 AF XY: 0.610 AC XY: 442302 AN XY: 724848

African (AFR) AF: 0.526 AC: 17547 AN: 33340

American (AMR) AF: 0.594 AC: 26420 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14729 AN: 26036

East Asian (EAS) AF: 0.597 AC: 23587 AN: 39512

South Asian (SAS) AF: 0.526 AC: 45210 AN: 85904

European-Finnish (FIN) AF: 0.708 AC: 37465 AN: 52942

Middle Eastern (MID) AF: 0.537 AC: 2983 AN: 5558

European-Non Finnish (NFE) AF: 0.621 AC: 688794 AN: 1109214

Other (OTH) AF: 0.595 AC: 35775 AN: 60122

GnomAD4 genome AF: 0.594 AC: 87874 AN: 148042 Hom.: 26317 Cov.: 25 AF XY: 0.595 AC XY: 42912 AN XY: 72066

African (AFR) AF: 0.534 AC: 21570 AN: 40424

American (AMR) AF: 0.577 AC: 8542 AN: 14804

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1958 AN: 3452

East Asian (EAS) AF: 0.587 AC: 2953 AN: 5032

South Asian (SAS) AF: 0.527 AC: 2506 AN: 4752

European-Finnish (FIN) AF: 0.718 AC: 6812 AN: 9494

Middle Eastern (MID) AF: 0.587 AC: 168 AN: 286

European-Non Finnish (NFE) AF: 0.624 AC: 41678 AN: 66840

Other (OTH) AF: 0.570 AC: 1168 AN: 2048

Alfa AF: 0.609 Hom.: 19354

Bravo AF: 0.584

Asia WGS AF: 0.525 AC: 1831 AN: 3478

EpiCase AF: 0.606

EpiControl AF: 0.606

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	-0.63
CADD	Benign	4.5
DANN	Benign	0.34
PhyloP100		0.27
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2044846; hg19: chr12-62778065; COSMIC: COSV108093875; COSMIC: COSV108093875;