3-122325324-C-G

Variant names:

• chr3-122325324-C-G
• rs750925495
• NM_005213.4:c.32C>G

Variant summary

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

The NM_005213.4(CSTA):​c.32C>G​(p.Pro11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSTA NM_005213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

Genes affected

CSTA (HGNC:2481): (cystatin A) 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 kininogens. This gene encodes a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer. [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 rank	MANE	Protein	UniProt
CSTA	NM_005213.4	c.32C>G	p.Pro11Arg	missense_variant	Exon 1 of 3	ENST00000264474.4	NP_005204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTA	ENST00000264474.4	c.32C>G	p.Pro11Arg	missense_variant	Exon 1 of 3	1	NM_005213.4	ENSP00000264474.3
CSTA	ENST00000479204.1	c.32C>G	p.Pro11Arg	missense_variant	Exon 1 of 2	2		ENSP00000418891.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.13	T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-7.9	D;D
REVEL	Benign	0.21
Sift	Benign	0.033	D;T
Sift4G	Benign	0.066	T;T
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.56		Loss of glycosylation at K10 (P = 0.0419);Loss of glycosylation at K10 (P = 0.0419);
MVP		0.74
MPC		0.58
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.62
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs750925495; hg19: chr3-122044171;