Variant 4-155953756-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001334.3(CTSO):c.92C>G(p.Pro31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,303,898 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 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

CTSO
NM_001334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.84

Variant links:

Genes affected

CTSO (HGNC:2542): (cathepsin O) The protein encoded by the gene is a cysteine proteinase and a member of the papain superfamily. This proteolytic enzyme is involved in cellular protein degradation and turnover. The recombinant form of this enzyme was shown to degrade synthetic peptides typically used as substrates for cysteine proteinases and its proteolytic activity was abolished by an inhibitor of cyteine proteinase. [provided by RefSeq, Jul 2008]

CTSO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049818724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSO	NM_001334.3 linkuse as main transcript	c.92C>G	p.Pro31Arg	missense_variant	1/8	ENST00000433477.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSO	ENST00000433477.4 linkuse as main transcript	c.92C>G	p.Pro31Arg	missense_variant	1/8	1	NM_001334.3	P2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00318

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

20832

Hom.:

AF XY:

0.0000788

AC XY:

AN XY:

12696

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:

0.000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000712

AC:

AN:

1151592

Hom.:

Cov.:

AF XY:

0.0000720

AC XY:

AN XY:

555666

show subpopulations

Gnomad4 AFR exome

AF:

0.000376

Gnomad4 AMR exome

AF:

0.0000829

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000782

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000553

Gnomad4 OTH exome

AF:

0.000258

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000962

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

Bravo

AF:

0.0000793

Asia WGS

AF:

0.000578

AC:

AN:

3476

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

May 04, 2022

The c.92C>G (p.P31R) alteration is located in exon 1 (coding exon 1) of the CTSO gene. This alteration results from a C to G substitution at nucleotide position 92, causing the proline (P) at amino acid position 31 to be replaced by an arginine (R). 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

0.053

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

Cadd

Benign

0.066

Dann

Benign

0.62

DEOGEN2

Benign

0.0089

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0014

M_CAP

Benign

0.019

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.26

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.3

REVEL

Benign

0.082

Sift

Benign

0.57

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.060

MutPred

0.41

Gain of MoRF binding (P = 0.0045);

MVP

0.43

MPC

0.055

ClinPred

0.053

GERP RS

-2.0

Varity_R

0.023

gMVP

0.18

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