dbSNP rs1420053115: USP37:p.Pro515Ser (chr2-218488351-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020935.3(USP37):c.1543C>T(p.Pro515Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

USP37
NM_020935.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.51

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08074334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP37	NM_020935.3 link	c.1543C>T	p.Pro515Ser	missense_variant	Exon 15 of 26	ENST00000258399.8	NP_065986.3	Q86T82-1A0A024R416

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP37	ENST00000258399.8 link	c.1543C>T	p.Pro515Ser	missense_variant	Exon 15 of 26	1	NM_020935.3	ENSP00000258399.3	Q86T82-1
USP37	ENST00000418019.5 link	c.1543C>T	p.Pro515Ser	missense_variant	Exon 15 of 26	1		ENSP00000396585.1	Q86T82-1
USP37	ENST00000415516.5 link	c.1327C>T	p.Pro443Ser	missense_variant	Exon 14 of 24	1		ENSP00000400902.1	Q86T82-2
USP37	ENST00000454775.5 link	c.1543C>T	p.Pro515Ser	missense_variant	Exon 15 of 26	2		ENSP00000393662.1	Q86T82-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0017

T;T;.;T

Eigen

Benign

-0.0035

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

.;.;D;D

M_CAP

Benign

0.0068

MetaRNN

Benign

0.081

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;.;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.61

N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.28

T;T;T;T

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.086

B;B;B;B

Vest4

0.36

MutPred

0.38

Gain of phosphorylation at P515 (P = 0.0078);Gain of phosphorylation at P515 (P = 0.0078);.;Gain of phosphorylation at P515 (P = 0.0078);

MVP

0.11

MPC

0.36

ClinPred

0.75

GERP RS

5.2

Varity_R

0.087

gMVP

0.16

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over