Variant 3-122337585-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005213.4(CSTA):c.105C>T(p.Tyr35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,608,798 control chromosomes in the GnomAD database, including 242,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 19820 hom., cov: 32)

Exomes 𝑓: 0.54 ( 223074 hom. )

Consequence

CSTA
NM_005213.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.785

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-122337585-C-T is Benign according to our data. Variant chr3-122337585-C-T is described in ClinVar as [Benign]. Clinvar id is 1297253.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-122337585-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.785 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 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.105C>T	p.Tyr35=	synonymous_variant	2/3	ENST00000264474.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSTA	ENST00000264474.4 linkuse as main transcript	c.105C>T	p.Tyr35=	synonymous_variant	2/3	1	NM_005213.4	P1
CSTA	ENST00000479204.1 linkuse as main transcript	c.105C>T	p.Tyr35=	synonymous_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75857

AN:

151906

Hom.:

19814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.0848

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.515

GnomAD3 exomes

AF:

0.499

AC:

125323

AN:

251220

Hom.:

33477

AF XY:

0.505

AC XY:

68558

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.512

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.0723

Gnomad SAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.574

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.545

AC:

793808

AN:

1456774

Hom.:

223074

Cov.:

AF XY:

0.544

AC XY:

394192

AN XY:

725052

show subpopulations

Gnomad4 AFR exome

AF:

0.398

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.0802

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.499

AC:

75879

AN:

152024

Hom.:

19820

Cov.:

AF XY:

0.496

AC XY:

36859

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.519

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.0846

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.577

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.553

Hom.:

44715

Bravo

AF:

0.493

Asia WGS

AF:

0.263

AC:

918

AN:

3478

EpiCase

AF:

0.580

EpiControl

AF:

0.581

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: 21412248, 18364739) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.39

DANN

Benign

0.15

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