chr1-55095286-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015306.3(USP24):c.6172G>A(p.Val2058Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000173 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
USP24
NM_015306.3 missense
NM_015306.3 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 3.69
Genes affected
USP24 (HGNC:12623): (ubiquitin specific peptidase 24) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036020517).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP24 | NM_015306.3 | c.6172G>A | p.Val2058Ile | missense_variant | 51/68 | ENST00000294383.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP24 | ENST00000294383.7 | c.6172G>A | p.Val2058Ile | missense_variant | 51/68 | 5 | NM_015306.3 | P1 | |
USP24 | ENST00000484447.6 | c.6172G>A | p.Val2058Ile | missense_variant | 51/68 | 3 | |||
USP24 | ENST00000482197.1 | n.34G>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000760 AC: 19AN: 250002Hom.: 1 AF XY: 0.0000740 AC XY: 10AN XY: 135154
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GnomAD4 exome AF: 0.000183 AC: 267AN: 1461348Hom.: 0 Cov.: 30 AF XY: 0.000190 AC XY: 138AN XY: 726906
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74470
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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 | Jun 24, 2022 | The c.6172G>A (p.V2058I) alteration is located in exon 51 (coding exon 51) of the USP24 gene. This alteration results from a G to A substitution at nucleotide position 6172, causing the valine (V) at amino acid position 2058 to be replaced by an isoleucine (I). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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