Variant chr3-122341557-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005213.4(CSTA):c.287C>T(p.Thr96Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,738 control chromosomes in the GnomAD database, including 15,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1161 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13963 hom. )

Consequence

CSTA
NM_005213.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79

Variant links:

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]

CSTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023583472).

BP6

Variant 3-122341557-C-T is Benign according to our data. Variant chr3-122341557-C-T is described in ClinVar as [Benign]. Clinvar id is 1232816.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSTA	NM_005213.4 linkuse as main transcript	c.287C>T	p.Thr96Met	missense_variant	3/3	ENST00000264474.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSTA	ENST00000264474.4 linkuse as main transcript	c.287C>T	p.Thr96Met	missense_variant	3/3	1	NM_005213.4	P1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16863

AN:

152072

Hom.:

1161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.0306

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.127

AC:

31915

AN:

251422

Hom.:

2367

AF XY:

0.134

AC XY:

18227

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.0931

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.0273

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.132

AC:

193422

AN:

1461548

Hom.:

13963

Cov.:

AF XY:

0.136

AC XY:

98629

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.0982

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.0200

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.111

AC:

16859

AN:

152190

Hom.:

1161

Cov.:

AF XY:

0.112

AC XY:

8304

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0409

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.0303

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.138

Hom.:

2426

Bravo

AF:

0.107

TwinsUK

AF:

0.133

AC:

494

ALSPAC

AF:

0.127

AC:

488

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.148

AC:

1277

ExAC

AF:

0.125

AC:

15156

Asia WGS

AF:

0.102

AC:

354

AN:

3478

EpiCase

AF:

0.146

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

This variant is associated with the following publications: (PMID: 17441792) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.2

DANN

Benign

0.97

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.26

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.037

Polyphen

0.86

Vest4

0.071

MPC

0.30

ClinPred

0.043

GERP RS

-7.3

Varity_R

0.14

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over