dbSNP rs780176473: USP37:p.Glu826Lys (chr2-218463357-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_020935.3(USP37):c.2476G>A(p.Glu826Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,461,780 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: not found (cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

USP37
NM_020935.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Publications

0 publications found

Variant links:

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]

USP37 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39574087).

BS2

High AC in GnomAdExome4 at 25 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020935.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP37	NM_020935.3	MANE Select	c.2476G>A	p.Glu826Lys	missense	Exon 22 of 26	NP_065986.3	Q86T82-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP37	ENST00000258399.8	TSL:1 MANE Select	c.2476G>A	p.Glu826Lys	missense	Exon 22 of 26	ENSP00000258399.3	Q86T82-1
USP37	ENST00000418019.5	TSL:1	c.2476G>A	p.Glu826Lys	missense	Exon 22 of 26	ENSP00000396585.1	Q86T82-1
USP37	ENST00000415516.5	TSL:1	c.2194G>A	p.Glu732Lys	missense	Exon 20 of 24	ENSP00000400902.1	Q86T82-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251422

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1111966

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.0091

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0040

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.8

PhyloP100

5.1

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.4

REVEL

Benign

0.21

Sift

Benign

0.14

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.53

MVP

0.16

MPC

0.44

ClinPred

0.95

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.30

Mutation Taster

=44/56

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over