12-62384200-A-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The ENST00000280377.10(USP15):āc.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
ENST00000280377.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.464
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 |
---|---|---|---|---|---|---|---|---|
USP15 | NM_001252078.2 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
USP15 | ENST00000280377.10 | c.1371A>G | p.Thr457= | synonymous_variant | 11/22 | 1 | NM_001252078.2 | ENSP00000280377 | P3 | |
USP15 | ENST00000353364.7 | c.1284A>G | p.Thr428= | synonymous_variant | 10/21 | 1 | ENSP00000258123 | A1 | ||
USP15 | ENST00000549268.1 | n.729A>G | non_coding_transcript_exon_variant | 4/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00136 AC: 206AN: 151804Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000415 AC: 104AN: 250874Hom.: 2 AF XY: 0.000280 AC XY: 38AN XY: 135610
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GnomAD4 exome AF: 0.000206 AC: 301AN: 1461168Hom.: 1 Cov.: 32 AF XY: 0.000162 AC XY: 118AN XY: 726846
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GnomAD4 genome AF: 0.00138 AC: 209AN: 151922Hom.: 2 Cov.: 32 AF XY: 0.00147 AC XY: 109AN XY: 74286
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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 provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 18, 2019 | This 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
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BayesDel_noAF
Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at