dbSNP rs61752208: USP37:p.Arg976His (chr2-218454943-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 38 hom. )

Consequence

USP37
NM_020935.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.33

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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/Likely_benign. ClinVar VariationId is 711264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 740 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.2927G>A	p.Arg976His	missense	Exon 26 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.2927G>A	p.Arg976His	missense	Exon 26 of 26	ENSP00000258399.3	Q86T82-1
USP37	ENST00000418019.5	TSL:1	c.2927G>A	p.Arg976His	missense	Exon 26 of 26	ENSP00000396585.1	Q86T82-1
USP37	ENST00000415516.5	TSL:1	c.2645G>A	p.Arg882His	missense	Exon 24 of 24	ENSP00000400902.1	Q86T82-2

Frequencies

GnomAD3 genomes

AF:

0.00486

AC:

739

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00641

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00619

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00520

AC:

1303

AN:

250632

AF XY:

0.00558

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00418

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00679

Gnomad NFE exome

AF:

0.00660

Gnomad OTH exome

AF:

0.00654

GnomAD4 exome

AF:

0.00572

AC:

8363

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

4228

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.000807

AC:

AN:

33470

American (AMR)

AF:

0.00474

AC:

212

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00413

AC:

108

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.00546

AC:

471

AN:

86250

European-Finnish (FIN)

AF:

0.00676

AC:

361

AN:

53382

Middle Eastern (MID)

AF:

0.00971

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00612

AC:

6802

AN:

1111988

Other (OTH)

AF:

0.00535

AC:

323

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

240

480

720

960

1200

<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

AF:

0.00486

AC:

740

AN:

152304

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41580

American (AMR)

AF:

0.0101

AC:

154

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00456

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00641

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00619

AC:

421

AN:

68018

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00573

Hom.:

Bravo

AF:

0.00440

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00533

AC:

647

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00741

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift

Benign

0.080

Sift4G

Uncertain

0.052

Polyphen

0.90

Vest4

0.17

MVP

0.48

MPC

0.54

ClinPred

0.015

GERP RS

3.8

Varity_R

0.038

gMVP

0.12

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over