Variant chr2-85616226-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006590.4(USP39):c.31G>A(p.Gly11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,484,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

USP39
NM_006590.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035565794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP39	NM_006590.4 linkuse as main transcript	c.31G>A	p.Gly11Ser	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.31G>A	p.Gly11Ser	missense_variant	1/13	1	NM_006590.4	ENSP00000312981.6		Q53GS9-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000914

AC:

AN:

131296

Hom.:

AF XY:

0.0000557

AC XY:

AN XY:

71872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000561

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:

0.0000319

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000375

AC:

AN:

1332706

Hom.:

Cov.:

AF XY:

0.0000353

AC XY:

AN XY:

650672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000366

Gnomad4 AMR exome

AF:

0.000759

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:

0.0000229

Gnomad4 OTH exome

AF:

0.0000548

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000877

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000590

AC:

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

Dec 27, 2023

The c.31G>A (p.G11S) alteration is located in exon 1 (coding exon 1) of the USP39 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the glycine (G) at amino acid position 11 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0076

T;T;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.74

T;.;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.036

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.17

N;N;N;N

REVEL

Benign

0.018

Sift

Benign

0.081

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.23

MutPred

0.25

Gain of phosphorylation at G11 (P = 0);Gain of phosphorylation at G11 (P = 0);Gain of phosphorylation at G11 (P = 0);Gain of phosphorylation at G11 (P = 0);

MVP

0.58

MPC

0.30

ClinPred

0.15

GERP RS

3.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.086

gMVP

0.52

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