20-24959666-T-G

Position:

• chr20-24959666-T-G

Variant summary

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

The NM_003650.4(CST7):​c.392T>G​(p.Val131Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CST7 NM_003650.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

Genes affected

CST7 (HGNC:2479): (cystatin F) The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. This gene encodes a glycosylated cysteine protease inhibitor with a putative role in immune regulation through inhibition of a unique target in the hematopoietic system. Expression of the protein has been observed in various human cancer cell lines established from malignant tumors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST7	NM_003650.4	c.392T>G	p.Val131Gly	missense_variant	4/4	ENST00000480798.2	NP_003641.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CST7	ENST00000480798.2	c.392T>G	p.Val131Gly	missense_variant	4/4	1	NM_003650.4	ENSP00000420384	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

May 15, 2024

The c.392T>G (p.V131G) alteration is located in exon 4 (coding exon 4) of the CST7 gene. This alteration results from a T to G substitution at nucleotide position 392, causing the valine (V) at amino acid position 131 to be replaced by a glycine (G). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.50		Loss of stability (P = 0.05);
MVP		0.42
MPC		0.40
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.93
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-24940302;