Variant 13-75560828-A-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_006002.5(UCHL3):c.130A>C(p.Met44Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000351 in 1,425,986 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: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

UCHL3
NM_006002.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

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:

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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=0.18284237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCHL3	NM_006002.5 linkuse as main transcript	c.130A>C	p.Met44Leu	missense_variant	3/9	ENST00000377595.8	NP_005993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCHL3	ENST00000377595.8 linkuse as main transcript	c.130A>C	p.Met44Leu	missense_variant	3/9	1	NM_006002.5	ENSP00000366819	P1
UCHL3	ENST00000471792.6 linkuse as main transcript	n.276A>C		non_coding_transcript_exon_variant	3/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1425986

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709148

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:

0.00000455

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 20, 2023

The c.130A>C (p.M44L) alteration is located in exon 3 (coding exon 3) of the UCHL3 gene. This alteration results from a A to C substitution at nucleotide position 130, causing the methionine (M) at amino acid position 44 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

0.25

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.27

.;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.14

Sift

Benign

0.50

.;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0

.;B

Vest4

0.30

MutPred

0.51

.;Gain of helix (P = 0.2059);

MVP

0.24

MPC

0.28

ClinPred

0.44

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over