9-87728350-CT-AC

Variant names:

• chr9-87728350-CT-AC
• NM_001912.5:c.350_351delCTinsAC
• CTSL p.Ser117Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001912.5(CTSL):​c.350_351delCTinsAC​(p.Ser117Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTSL NM_001912.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• Publications: 0 publications found

Genes affected

CTSL (HGNC:2537): (cathepsin L) The protein encoded by this gene is a lysosomal cysteine proteinase that plays a major role in intracellular protein catabolism. Its substrates include collagen and elastin, as well as alpha-1 protease inhibitor, a major controlling element of neutrophil elastase activity. The encoded protein has been implicated in several pathologic processes, including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria. This protein, which is a member of the peptidase C1 family, is a dimer composed of disulfide-linked heavy and light chains, both produced from a single protein precursor. Additionally, this protein cleaves the S1 subunit of the SARS-CoV-2 spike protein, which is necessary for entry of the virus into the cell. [provided by RefSeq, Aug 2020]

ENSG00000304058 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001912.5. 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
	CTSL	NM_001912.5	MANE Select	c.350_351delCTinsAC	p.Ser117Tyr	missense	N/A	NP_001903.1	P07711-1
	CTSL	NM_001257971.2		c.350_351delCTinsAC	p.Ser117Tyr	missense	N/A	NP_001244900.1	P07711-1
	CTSL	NM_001257972.2		c.350_351delCTinsAC	p.Ser117Tyr	missense	N/A	NP_001244901.1	P07711-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSL	ENST00000343150.10	TSL:1 MANE Select	c.350_351delCTinsAC	p.Ser117Tyr	missense	N/A	ENSP00000345344.5	P07711-1
	CTSL	ENST00000340342.11	TSL:1	c.350_351delCTinsAC	p.Ser117Tyr	missense	N/A	ENSP00000365061.5	P07711-1
	CTSL	ENST00000495822.2	TSL:1	n.459_460delCTinsAC		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-90343265;