Variant 20-45891598-CCTGCTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_000308.4(CTSA):c.51_56delGCTGCT(p.Leu18_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 0.0000677 in 1,506,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

CTSA
NM_000308.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

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 Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 20-45891598-CCTGCTG-C is Benign according to our data. Variant chr20-45891598-CCTGCTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 459631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSA	NM_000308.4 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	2/15	ENST00000646241.3	NP_000299.3	P10619-1X6R8A1
CTSA	NM_001127695.3 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	2/15		NP_001121167.1	P10619-1
CTSA	NM_001167594.3 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	2/14		NP_001161066.2	P10619-2B4E324X6R5C5
CTSA	NR_133656.2 link	n.96_101delGCTGCT		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSA	ENST00000646241.3 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	2/15		NM_000308.4	ENSP00000493613.2		P10619-1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000976

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000417

AC:

AN:

203638

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

112766

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000205

Gnomad SAS exome

AF:

0.0000377

Gnomad FIN exome

AF:

0.00218

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.000392

GnomAD4 exome

AF:

0.0000737

AC:

100

AN:

1356660

Hom.:

AF XY:

0.0000696

AC XY:

AN XY:

674970

show subpopulations

Gnomad4 AFR exome

AF:

0.0000647

Gnomad4 AMR exome

AF:

0.0000744

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000381

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.0000376

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149832

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73032

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000976

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined deficiency of sialidase AND beta galactosidase

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

CTSA-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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