12-62384200-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The ENST00000280377.10(USP15):ā€‹c.1371A>Gā€‹(p.Thr457=) 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: š‘“ 0.0014 ( 2 hom., cov: 32)
Exomes š‘“: 0.00021 ( 1 hom. )

Consequence

USP15
ENST00000280377.10 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.464
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
USP15NM_001252078.2 linkuse as main transcriptc.1371A>G p.Thr457= synonymous_variant 11/22 ENST00000280377.10 NP_001239007.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USP15ENST00000280377.10 linkuse as main transcriptc.1371A>G p.Thr457= synonymous_variant 11/221 NM_001252078.2 ENSP00000280377 P3Q9Y4E8-1
USP15ENST00000353364.7 linkuse as main transcriptc.1284A>G p.Thr428= synonymous_variant 10/211 ENSP00000258123 A1Q9Y4E8-2
USP15ENST00000549268.1 linkuse as main transcriptn.729A>G non_coding_transcript_exon_variant 4/75

Frequencies

GnomAD3 genomes
AF:
0.00136
AC:
206
AN:
151804
Hom.:
2
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.000415
AC:
104
AN:
250874
Hom.:
2
AF XY:
0.000280
AC XY:
38
AN XY:
135610
show subpopulations
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 SAS exome
AF:
0.0000327
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00574
Gnomad4 AMR exome
AF:
0.000582
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000396
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.00138
AC:
209
AN:
151922
Hom.:
2
Cov.:
32
AF XY:
0.00147
AC XY:
109
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.00458
Gnomad4 AMR
AF:
0.000985
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00190
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

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

USP15-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJun 18, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
7.5
DANN
Benign
0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs36011077; hg19: chr12-62777981; API