chr17-63477146-CTGCTGT-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate
The NM_000789.4(ACE):c.58_63del(p.Leu21_Leu22del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000775 in 1,291,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 7.7e-7 ( 0 hom. )
Consequence
ACE
NM_000789.4 inframe_deletion
NM_000789.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
ACE (HGNC:2707): (angiotensin I converting enzyme) This gene encodes an enzyme involved in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This angiotensin converting enzyme (ACE) also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored membrane proteins in spermatozoa. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms. [provided by RefSeq, Sep 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a signal_peptide (size 28) in uniprot entity ACE_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_000789.4
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-63477146-CTGCTGT-C is Pathogenic according to our data. Variant chr17-63477146-CTGCTGT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 871759.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACE | NM_000789.4 | c.58_63del | p.Leu21_Leu22del | inframe_deletion | 1/25 | ENST00000290866.10 | |
ACE | NM_001382700.1 | c.-178_-173del | 5_prime_UTR_variant | 1/22 | |||
ACE | NM_001382701.1 | c.-557_-552del | 5_prime_UTR_variant | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACE | ENST00000290866.10 | c.58_63del | p.Leu21_Leu22del | inframe_deletion | 1/25 | 1 | NM_000789.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 7.75e-7 AC: 1AN: 1291026Hom.: 0 AF XY: 0.00000157 AC XY: 1AN XY: 636292
GnomAD4 exome
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1291026
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AN XY:
636292
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2020 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at