3-179721405-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003940.3(USP13):c.904G>A(p.Glu302Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
USP13
NM_003940.3 missense
NM_003940.3 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 7.72
Genes affected
USP13 (HGNC:12611): (ubiquitin specific peptidase 13) Enables several functions, including BAT3 complex binding activity; chaperone binding activity; and cysteine-type peptidase activity. Involved in several processes, including maintenance of unfolded protein involved in ERAD pathway; regulation of cellular catabolic process; and regulation of transcription, DNA-templated. Acts upstream of or within protein deubiquitination and protein stabilization. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28570217).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP13 | NM_003940.3 | c.904G>A | p.Glu302Lys | missense_variant | 8/21 | ENST00000263966.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP13 | ENST00000263966.8 | c.904G>A | p.Glu302Lys | missense_variant | 8/21 | 1 | NM_003940.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250296Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135246
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461054Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726782
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 21, 2022 | The c.904G>A (p.E302K) alteration is located in exon 8 (coding exon 8) of the USP13 gene. This alteration results from a G to A substitution at nucleotide position 904, causing the glutamic acid (E) at amino acid position 302 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of ubiquitination at E302 (P = 0.0048);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at