dbSNP rs915264073: CTSO:p.Ala97Thr (chr4-155942412-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001334.3(CTSO):c.289G>A(p.Ala97Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,579,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CTSO
NM_001334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.699

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045036435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSO	NM_001334.3	MANE Select	c.289G>A	p.Ala97Thr	missense	Exon 3 of 8	NP_001325.1	P43234

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTSO	ENST00000433477.4	TSL:1 MANE Select	c.289G>A	p.Ala97Thr	missense	Exon 3 of 8	ENSP00000414904.3	P43234
CTSO	ENST00000679996.1		c.289G>A	p.Ala97Thr	missense	Exon 3 of 9	ENSP00000505550.1	A0A7P0T996
CTSO	ENST00000680741.1		c.289G>A	p.Ala97Thr	missense	Exon 3 of 8	ENSP00000505756.1	A0A7P0Z4C4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151834

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000884

AC:

AN:

226206

AF XY:

0.00000811

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000346

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000955

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1428034

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

710188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31554

American (AMR)

AF:

0.0000251

AC:

AN:

39890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25288

East Asian (EAS)

AF:

0.00

AC:

AN:

36770

South Asian (SAS)

AF:

0.00

AC:

AN:

81000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.0000164

AC:

AN:

1096356

Other (OTH)

AF:

0.00

AC:

AN:

58890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

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:

0.0000132

AC:

AN:

151834

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

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

Benign

0.065

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.5

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.019

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.031

M_CAP

Benign

0.0046

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

PhyloP100

-0.70

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.71

REVEL

Benign

0.069

Sift

Benign

0.48

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.14

MutPred

0.24

Gain of glycosylation at S96 (P = 0.0182)

MVP

0.20

MPC

0.052

ClinPred

0.038

GERP RS

0.36

Varity_R

0.039

gMVP

0.26

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over