1-206012534-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001910.4(CTSE):c.901A>C(p.Ile301Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,613,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 1 hom. )
Consequence
CTSE
NM_001910.4 missense
NM_001910.4 missense
Scores
1
1
6
Clinical Significance
Conservation
PhyloP100: 3.89
Genes affected
CTSE (HGNC:2530): (cathepsin E) This gene encodes a member of the A1 family of peptidases. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme, an aspartic endopeptidase, may be involved in antigen processing and the maturation of secretory proteins. Elevated expression of this gene has been observed in neurodegeneration. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3372541).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSE | NM_001910.4 | c.901A>C | p.Ile301Leu | missense_variant | 7/9 | ENST00000358184.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSE | ENST00000358184.7 | c.901A>C | p.Ile301Leu | missense_variant | 7/9 | 1 | NM_001910.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251238Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135788
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461788Hom.: 1 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727196
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74270
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.901A>C (p.I301L) alteration is located in exon 7 (coding exon 7) of the CTSE gene. This alteration results from a A to C substitution at nucleotide position 901, causing the isoleucine (I) at amino acid position 301 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Benign
LIST_S2
Benign
T
MetaRNN
Benign
T
PROVEAN
Benign
N
Sift
Benign
T
Sift4G
Uncertain
D
Vest4
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at