CTSO p.Gly172Arg

Variant names:

• chr4-155939409-C-G
• NM_001334.3:c.514G>C
• CTSO p.Gly172Arg

Your query was ambiguous. Multiple possible variants found:

• chr4-155939409-C-G
• chr4-155939409-C-T
• chr4-155939407-TCC-ACG
• chr4-155939407-TCC-GCG
• chr4-155939407-TCC-CCG
• chr4-155939407-TCC-CCT

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001334.3(CTSO):​c.514G>C​(p.Gly172Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTSO NM_001334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.60
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993

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.514G>C	p.Gly172Arg	missense	Exon 4 of 8	NP_001325.1	P43234

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSO	ENST00000433477.4	TSL:1 MANE Select	c.514G>C	p.Gly172Arg	missense	Exon 4 of 8	ENSP00000414904.3	P43234
	CTSO	ENST00000679996.1		c.514G>C	p.Gly172Arg	missense	Exon 4 of 9	ENSP00000505550.1	A0A7P0T996
	CTSO	ENST00000680741.1		c.514G>C	p.Gly172Arg	missense	Exon 4 of 8	ENSP00000505756.1	A0A7P0Z4C4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.88	D
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.085	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.91
gMVP		0.94
Mutation Taster		=14/86	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-156860561;