9-97037329-G-T

Position:

• chr9-97037329-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001333.4(CTSV):​c.319C>A​(p.Arg107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CTSV NM_001333.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

Genes affected

CTSV (HGNC:2538): (cathepsin V) The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that may play an important role in corneal physiology. This gene is expressed in colorectal and breast carcinomas but not in normal colon, mammary gland, or peritumoral tissues, suggesting a possible role for this gene in tumor processes. Alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07198903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSV	NM_001333.4	c.319C>A	p.Arg107Ser	missense_variant	4/8	ENST00000259470.6	NP_001324.2
CTSV	NM_001201575.2	c.319C>A	p.Arg107Ser	missense_variant	4/8		NP_001188504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSV	ENST00000259470.6	c.319C>A	p.Arg107Ser	missense_variant	4/8	1	NM_001333.4	ENSP00000259470	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.319C>A (p.R107S) alteration is located in exon 4 (coding exon 3) of the CTSV gene. This alteration results from a C to A substitution at nucleotide position 319, causing the arginine (R) at amino acid position 107 to be replaced by a serine (S). 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	0.26
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.62
DEOGEN2	Benign	0.044	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.12	T;.
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.24	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.0070
Sift	Benign	0.43	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.18	B;B
Vest4		0.21
MutPred		0.36		Loss of methylation at K104 (P = 0.0473);Loss of methylation at K104 (P = 0.0473);
MVP		0.47
MPC		0.14
ClinPred		0.22	T
GERP RS		1.9
Varity_R		0.15
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs768347914; hg19: chr9-99799611; COSMIC: COSV99414381;