20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

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

The NM_000308.4(CTSA):​c.51_56dupGCTGCT​(p.Leu18_Leu19dup) variant causes a disruptive 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 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSA	NM_000308.4	c.51_56dupGCTGCT	p.Leu18_Leu19dup	disruptive_inframe_insertion	2/15	ENST00000646241.3	NP_000299.3
CTSA	NM_001127695.3	c.51_56dupGCTGCT	p.Leu18_Leu19dup	disruptive_inframe_insertion	2/15		NP_001121167.1
CTSA	NM_001167594.3	c.51_56dupGCTGCT	p.Leu18_Leu19dup	disruptive_inframe_insertion	2/14		NP_001161066.2
CTSA	NR_133656.2	n.96_101dupGCTGCT		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSA	ENST00000646241.3	c.51_56dupGCTGCT	p.Leu18_Leu19dup	disruptive_inframe_insertion	2/15		NM_000308.4	ENSP00000493613.2

Frequencies

GnomAD3 genomes AF: 0.0000334 AC: 5 AN: 149796 Hom.: 0 Cov.: 0

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: 85 AN: 1432032 Hom.: 0 Cov.: 0 AF XY: 0.0000687 AC XY: 49 AN XY: 712840

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: 5 AN: 149910 Hom.: 0 Cov.: 0 AF XY: 0.0000274 AC XY: 2 AN XY: 73072

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

Submissions by phenotype

Combined deficiency of sialidase AND beta galactosidase Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72555383; hg19: chr20-44520237;