Variant 20-23605729-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001008693.3(CST9):c.136A>G(p.Met46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 1,614,216 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 25 hom. )

Consequence

CST9
NM_001008693.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.745

Variant links:

Genes affected

CST9 (HGNC:13261): (cystatin 9) 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 the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a secreted protein that may play a role in hematopoietic differentiation or inflammation. [provided by RefSeq, Jul 2008]

CST9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076812506).

BP6

Variant 20-23605729-T-C is Benign according to our data. Variant chr20-23605729-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2652241.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST9	NM_001008693.3 linkuse as main transcript	c.136A>G	p.Met46Val	missense_variant	1/2	ENST00000376971.4	NP_001008693.2	Q5W186

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CST9	ENST00000376971.4 linkuse as main transcript	c.136A>G	p.Met46Val	missense_variant	1/2	1	NM_001008693.3	ENSP00000366170.4		Q5W186

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

614

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00579

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00458

AC:

1153

AN:

251496

Hom.:

AF XY:

0.00519

AC XY:

706

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00480

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.00625

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00556

AC:

8121

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

3973

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00463

Gnomad4 FIN exome

AF:

0.00391

Gnomad4 NFE exome

AF:

0.00611

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.00403

AC:

614

AN:

152342

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

305

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00579

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00582

Hom.:

Bravo

AF:

0.00406

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00467

AC:

567

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00557

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

CST9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.16

DANN

Benign

0.35

DEOGEN2

Benign

0.0046

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.18

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.060

REVEL

Benign

0.033

Sift

Benign

0.12

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.090

MVP

0.14

MPC

0.042

ClinPred

0.0070

GERP RS

-1.9

Varity_R

0.072

gMVP

0.39

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