Variant 13-75566785-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000377595.8(UCHL3):c.274A>G(p.Ser92Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,611,686 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

UCHL3
ENST00000377595.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92

Variant links:

Genes affected

UCHL3 (HGNC:12515): (ubiquitin C-terminal hydrolase L3) The protein encoded by this gene is a member of the deubiquitinating enzyme family. Members of this family are proteases that catalyze the removal of ubiquitin from polypeptides and are divided into five classes, depending on the mechanism of catalysis. This protein may hydrolyze the ubiquitinyl-N-epsilon amide bond of ubiquitinated proteins to regenerate ubiquitin for another catalytic cycle. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

UCHL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27235454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCHL3	NM_006002.5 linkuse as main transcript	c.274A>G	p.Ser92Gly	missense_variant	4/9	ENST00000377595.8	NP_005993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
UCHL3	ENST00000377595.8 linkuse as main transcript	c.274A>G	p.Ser92Gly	missense_variant	4/9	1	NM_006002.5	ENSP00000366819	P1
UCHL3	ENST00000419068.1 linkuse as main transcript	c.76A>G	p.Ser26Gly	missense_variant	1/7	5		ENSP00000398189
UCHL3	ENST00000471792.6 linkuse as main transcript	n.420A>G		non_coding_transcript_exon_variant	4/7	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249044

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459476

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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 01, 2022

The c.274A>G (p.S92G) alteration is located in exon 4 (coding exon 4) of the UCHL3 gene. This alteration results from a A to G substitution at nucleotide position 274, causing the serine (S) at amino acid position 92 to be replaced by a glycine (G). 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

0.065

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.12

.;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

.;N;.

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.090

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.87

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.15

MutPred

0.54

.;Loss of methylation at K88 (P = 0.1607);.;

MVP

0.32

MPC

0.27

ClinPred

0.77

GERP RS

5.9

Varity_R

0.40

gMVP

0.22

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