20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000308.4(CTSA):c.54_56delGCT(p.Leu19del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,575,580 control chromosomes in the GnomAD database, including 278,356 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 31868 hom., cov: 0)

Exomes 𝑓: 0.61 ( 246488 hom. )

Consequence

CTSA
NM_000308.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 2.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 20-45891598-CCTG-C is Benign according to our data. Variant chr20-45891598-CCTG-C is described in ClinVar as [Benign]. Clinvar id is 195059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-45891598-CCTG-C is described in Lovd as [Benign]. Variant chr20-45891598-CCTG-C is described in Lovd as [Likely_benign]. Variant chr20-45891598-CCTG-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSA	NM_000308.4 link	c.54_56delGCT	p.Leu19del	disruptive_inframe_deletion	Exon 2 of 15	ENST00000646241.3	NP_000299.3	P10619-1X6R8A1
CTSA	NM_001127695.3 link	c.54_56delGCT	p.Leu19del	disruptive_inframe_deletion	Exon 2 of 15		NP_001121167.1	P10619-1
CTSA	NM_001167594.3 link	c.54_56delGCT	p.Leu19del	disruptive_inframe_deletion	Exon 2 of 14		NP_001161066.2	P10619-2B4E324X6R5C5
CTSA	NR_133656.2 link	n.99_101delGCT		non_coding_transcript_exon_variant	Exon 2 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSA	ENST00000646241.3 link	c.54_56delGCT	p.Leu19del	disruptive_inframe_deletion	Exon 2 of 15		NM_000308.4	ENSP00000493613.2		P10619-1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

98069

AN:

149708

Hom.:

31815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.642

GnomAD3 exomes

AF:

0.623

AC:

126967

AN:

203638

Hom.:

37576

AF XY:

0.620

AC XY:

69969

AN XY:

112766

show subpopulations

Gnomad AFR exome

AF:

0.659

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.485

Gnomad EAS exome

AF:

0.590

Gnomad SAS exome

AF:

0.623

Gnomad FIN exome

AF:

0.664

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.603

GnomAD4 exome

AF:

0.607

AC:

865716

AN:

1425758

Hom.:

246488

AF XY:

0.606

AC XY:

430222

AN XY:

709556

show subpopulations

Gnomad4 AFR exome

AF:

0.648

Gnomad4 AMR exome

AF:

0.666

Gnomad4 ASJ exome

AF:

0.499

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.609

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.655

AC:

98180

AN:

149822

Hom.:

31868

Cov.:

AF XY:

0.657

AC XY:

47994

AN XY:

73024

show subpopulations

Gnomad4 AFR

AF:

0.687

Gnomad4 AMR

AF:

0.706

Gnomad4 ASJ

AF:

0.532

Gnomad4 EAS

AF:

0.616

Gnomad4 SAS

AF:

0.657

Gnomad4 FIN

AF:

0.681

Gnomad4 NFE

AF:

0.631

Gnomad4 OTH

AF:

0.645

Bravo

AF:

0.668

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 19, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 06, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 64% of total chromosomes in ExAC -

not provided

Benign:4

Nov 22, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: flagged submission

Collection Method: clinical testing

Variant summary: The CTSA c.108_110delGCT (p.Leu37del) variant involves the deletion of a luecine in a string of 9 leucines. One in silico tool predicts a polymorphism outcome for this variant. This variant was found in 144801/230752 control chromosomes (43432 homozygotes) at a frequency of 0.6275179, which is approximately 397 times the estimated maximal expected allele frequency of a pathogenic CTSA variant (0.0015811), suggesting this variant is likely a benign polymorphism. Taken together, this variant is classified as benign. One case report cites the variant in a GSL patient, along with two other variants that have not been reported by other clinical labs, therefore it is unclear which variants are disease-causing. Multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. -

Mar 15, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Combined deficiency of sialidase AND beta galactosidase

Benign:4

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Latino/Admixed American population allele frequency is 68.93%% (rs781707830, 126967/203638 alleles, 37576 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.1.0, this variant is classified as BENIGN. Following criteria are met: BA1 -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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