Variant chr2-85616352-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006590.4(USP39):c.157G>C(p.Glu53Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000662 in 1,601,852 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

USP39
NM_006590.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

USP39 (HGNC:20071): (ubiquitin specific peptidase 39) Predicted to enable thiol-dependent deubiquitinase and zinc ion binding activity. Involved in spliceosomal complex assembly. Located in nucleoplasm. Part of U4/U6 x U5 tri-snRNP complex. [provided by Alliance of Genome Resources, Apr 2022]

USP39 links:

USP39 (HGNC:):

USP39 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=0.18211034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP39	NM_006590.4 linkuse as main transcript	c.157G>C	p.Glu53Gln	missense_variant	1/13	ENST00000323701.11	NP_006581.2	Q53GS9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP39	ENST00000323701.11 linkuse as main transcript	c.157G>C	p.Glu53Gln	missense_variant	1/13	1	NM_006590.4	ENSP00000312981.6		Q53GS9-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000137

AC:

AN:

219440

Hom.:

AF XY:

0.00000826

AC XY:

AN XY:

121000

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000209

Gnomad OTH exome

AF:

0.000187

GnomAD4 exome

AF:

0.0000676

AC:

AN:

1449656

Hom.:

Cov.:

AF XY:

0.0000597

AC XY:

AN XY:

720062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000390

Gnomad4 NFE exome

AF:

0.0000822

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000103

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.00000840

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.157G>C (p.E53Q) alteration is located in exon 1 (coding exon 1) of the USP39 gene. This alteration results from a G to C substitution at nucleotide position 157, causing the glutamic acid (E) at amino acid position 53 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0098

T;T;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

T;.;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.68

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.048

D;T;T;D

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.66

P;P;P;.

Vest4

0.36

MVP

0.58

MPC

0.23

ClinPred

0.64

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.23

gMVP

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over