19-55678686-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001130072.2(EPN1):āc.59C>Gā(p.Ala20Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Consequence
EPN1
NM_001130072.2 missense
NM_001130072.2 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 7.74
Genes affected
EPN1 (HGNC:21604): (epsin 1) This gene encodes a member of the epsin protein family. The encoded protein binds clathrin and is involved in the endocytosis of clathrin-coated vesicles. Loss of function of this gene is associated with reduced tumor growth and progression in certain cancer types. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.783
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPN1 | NM_001130072.2 | c.59C>G | p.Ala20Gly | missense_variant | 2/11 | ENST00000270460.11 | |
EPN1 | NM_001130071.2 | c.392C>G | p.Ala131Gly | missense_variant | 3/11 | ||
EPN1 | NM_001321263.2 | c.59C>G | p.Ala20Gly | missense_variant | 2/11 | ||
EPN1 | NM_013333.4 | c.59C>G | p.Ala20Gly | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPN1 | ENST00000270460.11 | c.59C>G | p.Ala20Gly | missense_variant | 2/11 | 2 | NM_001130072.2 | P3 | |
EPN1 | ENST00000411543.6 | c.392C>G | p.Ala131Gly | missense_variant | 3/11 | 1 | |||
EPN1 | ENST00000085079.11 | c.59C>G | p.Ala20Gly | missense_variant | 2/10 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250156Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135542
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GnomAD4 exome Cov.: 32
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74336
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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 | Feb 21, 2024 | The c.392C>G (p.A131G) alteration is located in exon 3 (coding exon 3) of the EPN1 gene. This alteration results from a C to G substitution at nucleotide position 392, causing the alanine (A) at amino acid position 131 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);.;
MVP
MPC
0.91
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