chr4-110491117-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001977.4(ENPEP):c.871G>C(p.Val291Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ENPEP
NM_001977.4 missense
NM_001977.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 8.68
Genes affected
ENPEP (HGNC:3355): (glutamyl aminopeptidase) The ENPEP gene encodes glutamyl aminopeptidase, a type II integral membrane protein with an extracellular zinc-binding domain. This protein can upregulate blood pressure by cleaving the N-terminal aspartate from angiotensin II, and can regulate blood vessel formation and enhance tumorigenesis in some tissues. Along with ANPEP and DPP4, ENPEP was found to be a candidate co-receptor for the coronavirus SARS-CoV-2, which causes COVID-19. [provided by RefSeq, Apr 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.964
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENPEP | NM_001977.4 | c.871G>C | p.Val291Leu | missense_variant | 3/20 | ENST00000265162.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENPEP | ENST00000265162.10 | c.871G>C | p.Val291Leu | missense_variant | 3/20 | 1 | NM_001977.4 | P1 | |
ENPEP | ENST00000510961.1 | n.299G>C | non_coding_transcript_exon_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250692Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135456
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459630Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726100
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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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 | Jul 12, 2022 | The c.871G>C (p.V291L) alteration is located in exon 3 (coding exon 3) of the ENPEP gene. This alteration results from a G to C substitution at nucleotide position 871, causing the valine (V) at amino acid position 291 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_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.0817);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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