X-15561954-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371415.1(ACE2):​c.2369A>G​(p.Glu790Gly) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

ACE2
NM_001371415.1 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
ACE2 (HGNC:13557): (angiotensin converting enzyme 2) The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23342013).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACE2NM_001371415.1 linkuse as main transcriptc.2369A>G p.Glu790Gly missense_variant 18/18 ENST00000252519.8 NP_001358344.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACE2ENST00000252519.8 linkuse as main transcriptc.2369A>G p.Glu790Gly missense_variant 18/181 NM_001371415.1 ENSP00000252519 P1Q9BYF1-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
23

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 submitterclinical testingAmbry GeneticsMay 14, 2024The c.2369A>G (p.E790G) alteration is located in exon 19 (coding exon 18) of the ACE2 gene. This alteration results from a A to G substitution at nucleotide position 2369, causing the glutamic acid (E) at amino acid position 790 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;T
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.76
.;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.5
M;M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.0
N;N
REVEL
Uncertain
0.33
Sift
Uncertain
0.021
D;D
Sift4G
Benign
0.25
T;T
Polyphen
0.39
B;B
Vest4
0.34
MutPred
0.14
Loss of stability (P = 0.0428);Loss of stability (P = 0.0428);
MVP
0.82
MPC
0.43
ClinPred
0.52
D
GERP RS
4.0
Varity_R
0.15
gMVP
0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-15580077; API