Genetic Variant CTSA:p.Leu14_Leu19del (chr20-45891598-CCTGCTGCTGCTGCTGCTG-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000308.4(CTSA):c.39_56delGCTGCTGCTGCTGCTGCT(p.Leu14_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 0.000000698 in 1,432,032 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CTSA
NM_000308.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSA	NM_000308.4 link	c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15	ENST00000646241.3	NP_000299.3	P10619-1X6R8A1
CTSA	NM_001127695.3 link	c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15		NP_001121167.1	P10619-1
CTSA	NM_001167594.3 link	c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 14		NP_001161066.2	P10619-2B4E324X6R5C5
CTSA	NR_133656.2 link	n.84_101delGCTGCTGCTGCTGCTGCT		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.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15		NM_000308.4	ENSP00000493613.2		P10619-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432032

Hom.:

AF XY:

0.00

AC XY:

AN XY:

712840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over