chr9-97037340-C-G

Variant names:

• chr9-97037340-C-G
• NM_001333.4:c.308G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001333.4(CTSV):​c.308G>C​(p.Gly103Ala) 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. 15/22 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: 2.81
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17075187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001333.4. 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
	CTSV	NM_001333.4	MANE Select	c.308G>C	p.Gly103Ala	missense	Exon 4 of 8	NP_001324.2
	CTSV	NM_001201575.2		c.308G>C	p.Gly103Ala	missense	Exon 4 of 8	NP_001188504.1	O60911

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSV	ENST00000259470.6	TSL:1 MANE Select	c.308G>C	p.Gly103Ala	missense	Exon 4 of 8	ENSP00000259470.5	O60911
	CTSV	ENST00000538255.6	TSL:1	c.249+153G>C		intron	N/A	ENSP00000445052.2	A0A804EQJ3
	CTSV	ENST00000679661.1		c.308G>C	p.Gly103Ala	missense	Exon 5 of 9	ENSP00000506713.1	O60911

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.54	N
PhyloP100		2.8
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.088
Sift	Benign	0.048	D
Sift4G	Uncertain	0.049	D
Polyphen		0.61	P
Vest4		0.21
MutPred		0.25		Loss of disorder (P = 0.0912)
MVP		0.40
MPC		0.31
ClinPred		0.89	D
GERP RS		2.9
Varity_R		0.35
gMVP		0.55
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr9-99799622;