Variant chr17-60183222-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032582.4(USP32):c.4066G>T(p.Val1356Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

USP32
NM_032582.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

Variant links:

Genes affected

USP32 (HGNC:19143): (ubiquitin specific peptidase 32) Enables thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

USP32 links:

USP32 (HGNC:):

USP32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052113026).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP32	NM_032582.4 linkuse as main transcript	c.4066G>T	p.Val1356Leu	missense_variant	31/34	ENST00000300896.9	NP_115971.2	Q8NFA0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
USP32	ENST00000300896.9 linkuse as main transcript	c.4066G>T	p.Val1356Leu	missense_variant	31/34	1	NM_032582.4	ENSP00000300896.3	Q8NFA0-1
USP32	ENST00000592339.5 linkuse as main transcript	c.3076G>T	p.Val1026Leu	missense_variant	23/26	1		ENSP00000467885.1	K7EQL6
USP32	ENST00000586238.1 linkuse as main transcript	n.706G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152202

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251086

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135686

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:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000883

AC:

129

AN:

1461660

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

727138

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:

0.000113

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 29, 2021

The c.4066G>T (p.V1356L) alteration is located in exon 31 (coding exon 31) of the USP32 gene. This alteration results from a G to T substitution at nucleotide position 4066, causing the valine (V) at amino acid position 1356 to be replaced by a leucine (L). 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

0.076

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.94

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.42

N;.

REVEL

Benign

0.016

Sift

Benign

0.27

T;.

Sift4G

Benign

0.49

T;T

Polyphen

0.0030

B;.

Vest4

0.21

MutPred

0.34

Loss of methylation at K1360 (P = 0.0693);.;

MVP

0.20

MPC

0.54

ClinPred

0.073

GERP RS

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.20

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