2-218454943-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_020935.3(USP37):c.2927G>A(p.Arg976His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,614,090 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0049 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0057 ( 38 hom. )
Consequence
USP37
NM_020935.3 missense
NM_020935.3 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 1.33
Genes affected
USP37 (HGNC:20063): (ubiquitin specific peptidase 37) Enables cysteine-type endopeptidase activity; protein kinase binding activity; and thiol-dependent deubiquitinase. Involved in G1/S transition of mitotic cell cycle; protein deubiquitination; and regulation of DNA replication. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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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 (MetaRNN=0.0056904554).
BP6
Variant 2-218454943-C-T is Benign according to our data. Variant chr2-218454943-C-T is described in ClinVar as [Benign]. Clinvar id is 711264.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 740 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP37 | NM_020935.3 | c.2927G>A | p.Arg976His | missense_variant | 26/26 | ENST00000258399.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP37 | ENST00000258399.8 | c.2927G>A | p.Arg976His | missense_variant | 26/26 | 1 | NM_020935.3 | P1 | |
USP37 | ENST00000418019.5 | c.2927G>A | p.Arg976His | missense_variant | 26/26 | 1 | P1 | ||
USP37 | ENST00000415516.5 | c.2645G>A | p.Arg882His | missense_variant | 24/24 | 1 | |||
USP37 | ENST00000454775.5 | c.2927G>A | p.Arg976His | missense_variant | 26/26 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00486 AC: 739AN: 152186Hom.: 5 Cov.: 33
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GnomAD3 exomes AF: 0.00520 AC: 1303AN: 250632Hom.: 7 AF XY: 0.00558 AC XY: 756AN XY: 135452
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GnomAD4 exome AF: 0.00572 AC: 8363AN: 1461786Hom.: 38 Cov.: 34 AF XY: 0.00581 AC XY: 4228AN XY: 727200
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GnomAD4 genome AF: 0.00486 AC: 740AN: 152304Hom.: 5 Cov.: 33 AF XY: 0.00510 AC XY: 380AN XY: 74472
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Uncertain
T;T;T;T
Polyphen
P;P;D;P
Vest4
MVP
MPC
ClinPred
T
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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