Variant 20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000308.4(CTSA):c.51_56dup(p.Leu18_Leu19dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

CTSA
NM_000308.4 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CTSA	NM_000308.4 linkuse as main transcript	c.51_56dup	p.Leu18_Leu19dup	inframe_insertion	2/15	ENST00000646241.3
CTSA	NM_001127695.3 linkuse as main transcript	c.51_56dup	p.Leu18_Leu19dup	inframe_insertion	2/15
CTSA	NM_001167594.3 linkuse as main transcript	c.51_56dup	p.Leu18_Leu19dup	inframe_insertion	2/14
CTSA	NR_133656.2 linkuse as main transcript	n.96_101dup		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSA	ENST00000646241.3 linkuse as main transcript	c.51_56dup	p.Leu18_Leu19dup	inframe_insertion	2/15		NM_000308.4		P10619-1

Frequencies

GnomAD3 genomes

AF:

0.0000334

AC:

AN:

149796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000594

AC:

AN:

1432032

Hom.:

Cov.:

AF XY:

0.0000687

AC XY:

AN XY:

712840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000459

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000334

AC:

AN:

149910

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

73072

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Combined deficiency of sialidase AND beta galactosidase

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jul 12, 2022

This variant, c.105_110dup, results in the insertion of 2 amino acid(s) of the CTSA protein (p.Leu36_Leu37dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CTSA-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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