Variant 1-193023941-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001199261.3(UCHL5):c.635G>C(p.Ser212Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000812 in 1,600,966 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: 0.0000083 ( 0 hom. )

Consequence

UCHL5
NM_001199261.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

Variant links:

Genes affected

UCHL5 (HGNC:19678): (ubiquitin C-terminal hydrolase L5) Enables endopeptidase inhibitor activity; proteasome binding activity; and thiol-dependent deubiquitinase. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of smoothened signaling pathway; and protein deubiquitination. Located in cytosol; nucleolus; and nucleoplasm. Colocalizes with Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

UCHL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34195936).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCHL5	NM_001199261.3 linkuse as main transcript	c.635G>C	p.Ser212Thr	missense_variant	8/11	ENST00000367454.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCHL5	ENST00000367454.6 linkuse as main transcript	c.635G>C	p.Ser212Thr	missense_variant	8/11	1	NM_001199261.3	A1	Q9Y5K5-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000828

AC:

AN:

1448792

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

721470

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:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

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 06, 2021

The c.635G>C (p.S212T) alteration is located in exon 8 (coding exon 8) of the UCHL5 gene. This alteration results from a G to C substitution at nucleotide position 635, causing the serine (S) at amino acid position 212 to be replaced by a threonine (T). 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

0.23

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.23

T;.;T;T;.;.;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.34

T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.8

L;L;.;.;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.10

T;T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T;T

Polyphen

0.0010

B;B;.;.;B;B;.

Vest4

0.36

MutPred

0.31

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;

MVP

0.31

MPC

0.58

ClinPred

0.82

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.76

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