Variant 20-45891283-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 ENST00000372484(CTSA):c.-43G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00951 in 1,522,640 control chromosomes in the GnomAD database, including 696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 66 hom., cov: 33)

Exomes 𝑓: 0.0090 ( 630 hom. )

Consequence

CTSA
ENST00000372484 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.315

Variant links:

Genes affected

CTSA (HGNC:9251): (cathepsin A) This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis. [provided by RefSeq, Nov 2015]

CTSA links:

CTSA (HGNC:):

CTSA 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 (BayesDel_noAF=-0.62).

BP6

Variant 20-45891283-G-T is Benign according to our data. Variant chr20-45891283-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 338522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.45891283G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
CTSA	ENST00000372484 linkuse as main transcript	c.-43G>T	5_prime_UTR_premature_start_codon_gain_variant	1/15	1	ENSP00000361562.3	X6R8A1
CTSA	ENST00000372484 linkuse as main transcript	c.-43G>T	5_prime_UTR_variant	1/15	1	ENSP00000361562.3	X6R8A1
CTSA	ENST00000677394 linkuse as main transcript	c.-43G>T	5_prime_UTR_premature_start_codon_gain_variant	2/16		ENSP00000504790.1	X6R8A1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2128

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0254

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0277

AC:

4251

AN:

153190

Hom.:

198

AF XY:

0.0254

AC XY:

2079

AN XY:

81808

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.0701

Gnomad ASJ exome

AF:

0.000947

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.0283

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.000696

Gnomad OTH exome

AF:

0.0191

GnomAD4 exome

AF:

0.00902

AC:

12355

AN:

1370304

Hom.:

630

Cov.:

AF XY:

0.00934

AC XY:

6327

AN XY:

677526

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.0624

Gnomad4 ASJ exome

AF:

0.000800

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.0290

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.000558

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0139

AC:

2124

AN:

152336

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1211

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.0362

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.0780

AC:

270

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	in vitro	Seelig Lab, University of Washington	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2019	- -

Combined deficiency of sialidase AND beta galactosidase

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.6

DANN

Benign

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over