Genetic Variant NM_006002.5:c.628A>G (chr13-75605747-A-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_006002.5(UCHL3):c.628A>G(p.Lys210Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000020 ( 0 hom. )

Consequence

UCHL3
NM_006002.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Publications

1 publications found

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:

ENSG00000261553 (HGNC:):

ENSG00000261553 links:

LMO7-AS1 (HGNC:50277): (LMO7 antisense RNA 1)

LMO7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31003308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006002.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UCHL3	NM_006002.5	MANE Select	c.628A>G	p.Lys210Glu	missense	Exon 9 of 9	NP_005993.1	A0A140VJZ4
UCHL3	NM_001270952.2		c.520A>G	p.Lys174Glu	missense	Exon 9 of 9	NP_001257881.1
LMO7-AS1	NR_120410.1		n.348-802T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UCHL3	ENST00000377595.8	TSL:1 MANE Select	c.628A>G	p.Lys210Glu	missense	Exon 9 of 9	ENSP00000366819.3	P15374
UCHL3	ENST00000963592.1		c.649A>G	p.Lys217Glu	missense	Exon 10 of 10	ENSP00000633651.1
UCHL3	ENST00000963593.1		c.634A>G	p.Lys212Glu	missense	Exon 10 of 10	ENSP00000633652.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000518

AC:

AN:

250908

AF XY:

0.0000664

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000336

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111946

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

M_CAP

Benign

0.011

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.3

PhyloP100

6.8

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.2

REVEL

Benign

0.25

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0090

Polyphen

0.33

Vest4

0.52

MutPred

0.47

Loss of methylation at K210 (P = 0.0012)

MVP

0.61

MPC

0.53

ClinPred

0.42

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.85

Mutation Taster

=52/48

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over