Variant chr2-218454943-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/19 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

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 made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 711264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 740 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP37	NM_020935.3 linkuse as main transcript	c.2927G>A	p.Arg976His	missense_variant	26/26	ENST00000258399.8	NP_065986.3	Q86T82-1A0A024R416

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
USP37	ENST00000258399.8 linkuse as main transcript	c.2927G>A	p.Arg976His	missense_variant	26/26	1	NM_020935.3	ENSP00000258399.3	Q86T82-1
USP37	ENST00000418019.5 linkuse as main transcript	c.2927G>A	p.Arg976His	missense_variant	26/26	1		ENSP00000396585.1	Q86T82-1
USP37	ENST00000415516.5 linkuse as main transcript	c.2645G>A	p.Arg882His	missense_variant	24/24	1		ENSP00000400902.1	Q86T82-2
USP37	ENST00000454775.5 linkuse as main transcript	c.2927G>A	p.Arg976His	missense_variant	26/26	2		ENSP00000393662.1	Q86T82-1

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

GnomAD3 exomes

AF:

0.00520

AC:

1303

AN:

250632

Hom.:

AF XY:

0.00558

AC XY:

756

AN XY:

135452

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 SAS exome

AF:

0.00480

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

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00546

Gnomad4 FIN exome

AF:

0.00676

Gnomad4 NFE exome

AF:

0.00612

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.00486

AC:

740

AN:

152304

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00641

Gnomad4 NFE

AF:

0.00619

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00606

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

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	USP37: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0053

T;T;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.76

.;.;T;T

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.080

T;T;T;T

Sift4G

Uncertain

0.052

T;T;T;T

Polyphen

0.90

P;P;D;P

Vest4

0.17

MVP

0.48

MPC

0.54

ClinPred

0.015

GERP RS

3.8

Varity_R

0.038

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over