Variant rs604630 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001335.4(CTSW):c.415A>G(p.Ser139Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,614,124 control chromosomes in the GnomAD database, including 788,721 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.94 ( 67445 hom., cov: 32)

Exomes 𝑓: 0.99 ( 721276 hom. )

Consequence

CTSW
NM_001335.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.913

Variant links:

Genes affected

CTSW (HGNC:2546): (cathepsin W) The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2. [provided by RefSeq, Jul 2008]

CTSW links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6164156E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSW	NM_001335.4 linkuse as main transcript	c.415A>G	p.Ser139Gly	missense_variant	4/10	ENST00000307886.8	NP_001326.3	P56202

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSW	ENST00000307886.8 linkuse as main transcript	c.415A>G	p.Ser139Gly	missense_variant	4/10	1	NM_001335.4	ENSP00000311300.3		P56202

Frequencies

GnomAD3 genomes

AF:

0.936

AC:

142446

AN:

152142

Hom.:

67405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.993

Gnomad AMR

AF:

0.969

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.948

GnomAD3 exomes

AF:

0.983

AC:

247185

AN:

251410

Hom.:

121888

AF XY:

0.988

AC XY:

134224

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.781

Gnomad AMR exome

AF:

0.988

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.991

GnomAD4 exome

AF:

0.993

AC:

1451250

AN:

1461864

Hom.:

721276

Cov.:

AF XY:

0.994

AC XY:

722679

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.772

Gnomad4 AMR exome

AF:

0.986

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.983

GnomAD4 genome

AF:

0.936

AC:

142544

AN:

152260

Hom.:

67445

Cov.:

AF XY:

0.940

AC XY:

69955

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.783

Gnomad4 AMR

AF:

0.969

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.949

Alfa

AF:

0.989

Hom.:

132919

Bravo

AF:

0.929

TwinsUK

AF:

0.999

AC:

3704

ALSPAC

AF:

0.999

AC:

3849

ESP6500AA

AF:

0.805

AC:

3544

ESP6500EA

AF:

0.999

AC:

8585

ExAC

AF:

0.980

AC:

118960

Asia WGS

AF:

0.988

AC:

3434

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.021

DANN

Benign

0.34

DEOGEN2

Benign

0.30

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.13

T;T;T

MetaRNN

Benign

0.0000016

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

3.1

N;N;N

REVEL

Benign

0.010

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.027

MPC

0.056

ClinPred

0.0018

GERP RS

-1.7

Varity_R

0.030

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over