1-206012350-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001910.4(CTSE):c.984C>T(p.Asn328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,613,960 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000070 ( 1 hom. )
Consequence
CTSE
NM_001910.4 synonymous
NM_001910.4 synonymous
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -0.844
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.049866945).
BP6
?
Variant 1-206012350-G-A is Benign according to our data. Variant chr1-206012350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2591757.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.844 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSE | NM_001910.4 | c.984C>T | p.Asn328= | synonymous_variant | 8/9 | ENST00000358184.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSE | ENST00000358184.7 | c.984C>T | p.Asn328= | synonymous_variant | 8/9 | 1 | NM_001910.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152104Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
23
AN:
152104
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251340Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135840
GnomAD3 exomes
AF:
AC:
22
AN:
251340
Hom.:
AF XY:
AC XY:
9
AN XY:
135840
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000698 AC: 102AN: 1461738Hom.: 1 Cov.: 31 AF XY: 0.0000633 AC XY: 46AN XY: 727164
GnomAD4 exome
AF:
AC:
102
AN:
1461738
Hom.:
Cov.:
31
AF XY:
AC XY:
46
AN XY:
727164
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74410
GnomAD4 genome
?
AF:
AC:
23
AN:
152222
Hom.:
Cov.:
33
AF XY:
AC XY:
12
AN XY:
74410
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
LIST_S2
Benign
T
MetaRNN
Benign
T
PROVEAN
Benign
N
Sift
Uncertain
D
Sift4G
Benign
T
Vest4
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at