Variant 3-122341543-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005213.4(CSTA):c.273G>T(p.Lys91Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,614,096 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 105 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 79 hom. )

Consequence

CSTA
NM_005213.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0440

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029422045).

BP6

Variant 3-122341543-G-T is Benign according to our data. Variant chr3-122341543-G-T is described in ClinVar as [Benign]. Clinvar id is 767925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 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.273G>T	p.Lys91Asn	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.273G>T	p.Lys91Asn	missense_variant	3/3	1	NM_005213.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2803

AN:

152138

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0636

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00478

AC:

1202

AN:

251442

Hom.:

AF XY:

0.00352

AC XY:

479

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0621

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00192

AC:

2809

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1154

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0651

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000746

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.0185

AC:

2814

AN:

152256

Hom.:

105

Cov.:

AF XY:

0.0186

AC XY:

1387

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0637

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00974

Hom.:

Bravo

AF:

0.0212

ESP6500AA

AF:

0.0579

AC:

255

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00581

AC:

706

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.33

Sift

Benign

0.037

Sift4G

Benign

0.10

Polyphen

0.95

Vest4

0.17

MutPred

0.46

Loss of ubiquitination at K91 (P = 0.0034);

MVP

0.87

MPC

0.55

ClinPred

0.044

GERP RS

3.6

Varity_R

0.80

gMVP

0.51

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