rs72555383

Variant names:

• chr20-45891598-CCTGCTGCTGCTGCTGCTG-C
• rs72555383
• NM_000308.4:c.39_56delGCTGCTGCTGCTGCTGCT

Your query was ambiguous. Multiple possible variants found:

• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
• chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CNNNNNNNNNNNNNNNNNNNNNNN

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• galactosialidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Illumina, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000308.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000308.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSA	NM_000308.4	MANE Select	c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15	NP_000299.3	P10619-1
	CTSA	NM_001127695.3		c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15	NP_001121167.1	P10619-1
	CTSA	NM_001167594.3		c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 14	NP_001161066.2	P10619-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSA	ENST00000646241.3	MANE Select	c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15	ENSP00000493613.2	P10619-1
	CTSA	ENST00000372484.8	TSL:1	c.93_110delGCTGCTGCTGCTGCTGCT	p.Leu32_Leu37del	disruptive_inframe_deletion	Exon 2 of 15	ENSP00000361562.3	X6R8A1
	CTSA	ENST00000191018.9	TSL:1	c.39_56delGCTGCTGCTGCTGCTGCT	p.Leu14_Leu19del	disruptive_inframe_deletion	Exon 2 of 15	ENSP00000191018.5	P10619-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432032 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 712840

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32872

American (AMR) AF: 0.00 AC: 0 AN: 43594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.00 AC: 0 AN: 39148

South Asian (SAS) AF: 0.00 AC: 0 AN: 84808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093902

Other (OTH) AF: 0.00 AC: 0 AN: 59254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs72555383; hg19: chr20-44520237;