chr12-62384200-A-G

Variant names:

• chr12-62384200-A-G
• rs36011077
• NM_001252078.2:c.1371A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001252078.2(USP15):​c.1371A>G​(p.Thr457Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,613,090 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: USP15 NM_001252078.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.464
• Publications: 0 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-62384200-A-G is Benign according to our data. Variant chr12-62384200-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3033240.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.464 with no splicing effect.
• BS2: High AC in GnomAd4 at 209 AD gene.

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.1371A>G	p.Thr457Thr	synonymous	Exon 11 of 22	NP_001239007.1	Q9Y4E8-1
	USP15	NM_006313.3		c.1284A>G	p.Thr428Thr	synonymous	Exon 10 of 21	NP_006304.1	Q9Y4E8-2
	USP15	NM_001351159.2		c.1008A>G	p.Thr336Thr	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.1371A>G	p.Thr457Thr	synonymous	Exon 11 of 22	ENSP00000280377.5	Q9Y4E8-1
	USP15	ENST00000353364.7	TSL:1	c.1284A>G	p.Thr428Thr	synonymous	Exon 10 of 21	ENSP00000258123.4	Q9Y4E8-2
	USP15	ENST00000957648.1		c.1494A>G	p.Thr498Thr	synonymous	Exon 12 of 23	ENSP00000627707.1

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 206 AN: 151804 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00452

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000987

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000415 AC: 104 AN: 250874 AF XY: 0.000280

Gnomad AFR exome AF: 0.00487

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000206 AC: 301 AN: 1461168 Hom.: 1 Cov.: 32 AF XY: 0.000162 AC XY: 118 AN XY: 726846

African (AFR) AF: 0.00574 AC: 192 AN: 33452

American (AMR) AF: 0.000582 AC: 26 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111566

Other (OTH) AF: 0.000580 AC: 35 AN: 60354

GnomAD4 genome AF: 0.00138 AC: 209 AN: 151922 Hom.: 2 Cov.: 32 AF XY: 0.00147 AC XY: 109 AN XY: 74286

African (AFR) AF: 0.00458 AC: 190 AN: 41528

American (AMR) AF: 0.000985 AC: 15 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67776

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.000816 Hom.: 0

Bravo AF: 0.00195

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely 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	-0.54
CADD	Benign	7.5
DANN	Benign	0.71
PhyloP100		0.46
Mutation Taster		=91/9	polymorphism

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: rs36011077; hg19: chr12-62777981;