rs181943893

Variant names:

• chr20-45891622-G-A
• rs181943893
• NM_000308.4:c.54G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-45891622-G-A
• chr20-45891622-G-C
• chr20-45891622-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000308.4(CTSA):​c.54G>A​(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTSA NM_000308.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 6 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen, Illumina

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=2.74 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSA	NM_000308.4	MANE Select	c.54G>A	p.Leu18Leu	synonymous	Exon 2 of 15	NP_000299.3
	CTSA	NM_001127695.3		c.54G>A	p.Leu18Leu	synonymous	Exon 2 of 15	NP_001121167.1
	CTSA	NM_001167594.3		c.54G>A	p.Leu18Leu	synonymous	Exon 2 of 14	NP_001161066.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSA	ENST00000646241.3	MANE Select	c.54G>A	p.Leu18Leu	synonymous	Exon 2 of 15	ENSP00000493613.2
	CTSA	ENST00000372484.8	TSL:1	c.108G>A	p.Leu36Leu	synonymous	Exon 2 of 15	ENSP00000361562.3
	CTSA	ENST00000191018.9	TSL:1	c.54G>A	p.Leu18Leu	synonymous	Exon 2 of 15	ENSP00000191018.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		2.7
PromoterAI		0.0097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs181943893; hg19: chr20-44520261; COSMIC: COSV51944911; COSMIC: COSV51944911;