NM_005213.4:c.280G>C

Variant names:

• chr3-122341550-G-C
• rs200394711
• NM_005213.4:c.280G>C

Variant summary

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

The NM_005213.4(CSTA):​c.280G>C​(p.Glu94Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CSTA NM_005213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71

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.280G>C	p.Glu94Gln	missense_variant	Exon 3 of 3	ENST00000264474.4	NP_005204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTA	ENST00000264474.4	c.280G>C	p.Glu94Gln	missense_variant	Exon 3 of 3	1	NM_005213.4	ENSP00000264474.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251444 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135890

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.19	D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.34
Sift	Benign	0.034	D
Sift4G	Benign	0.094	T
Polyphen		1.0	D
Vest4		0.22
MutPred		0.34		Gain of glycosylation at T96 (P = 0.0514);
MVP		0.88
MPC		0.55
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.57

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: rs200394711; hg19: chr3-122060397;