1-8865290-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate

The NM_001428.5(ENO1):ā€‹c.860A>Cā€‹(p.Tyr287Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,930 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‘“ 0.00014 ( 0 hom., cov: 32)
Exomes š‘“: 0.000049 ( 0 hom. )

Consequence

ENO1
NM_001428.5 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
Variant links:
Genes affected
ENO1 (HGNC:3350): (enolase 1) This gene encodes alpha-enolase, one of three enolase isoenzymes found in mammals. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy. [provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1
In a modified_residue Phosphotyrosine (size 0) in uniprot entity ENOA_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENO1NM_001428.5 linkuse as main transcriptc.860A>C p.Tyr287Ser missense_variant 8/12 ENST00000234590.10 NP_001419.1 P06733-1A0A024R4F1
ENO1NM_001353346.3 linkuse as main transcriptc.860A>C p.Tyr287Ser missense_variant 8/12 NP_001340275.1
ENO1NM_001201483.4 linkuse as main transcriptc.581A>C p.Tyr194Ser missense_variant 7/11 NP_001188412.1 P06733-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENO1ENST00000234590.10 linkuse as main transcriptc.860A>C p.Tyr287Ser missense_variant 8/121 NM_001428.5 ENSP00000234590.4 P06733-1

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251068
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135744
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000347
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1461826
Hom.:
0
Cov.:
31
AF XY:
0.0000564
AC XY:
41
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000106
ExAC
AF:
0.0000247
AC:
3

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 GeneticsJan 26, 2022The c.860A>C (p.Y287S) alteration is located in exon 8 (coding exon 7) of the ENO1 gene. This alteration results from a A to C substitution at nucleotide position 860, causing the tyrosine (Y) at amino acid position 287 to be replaced by a serine (S). 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
Pathogenic
0.79
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.72
D;D;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.89
D;D;D
MetaSVM
Uncertain
0.48
D
MutationAssessor
Pathogenic
4.8
H;H;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-6.8
D;.;.
REVEL
Pathogenic
0.76
Sift
Pathogenic
0.0
D;.;.
Sift4G
Uncertain
0.0030
D;.;.
Polyphen
0.99
D;D;.
Vest4
0.90
MutPred
0.78
Gain of disorder (P = 0.0098);Gain of disorder (P = 0.0098);Gain of disorder (P = 0.0098);
MVP
0.92
MPC
1.2
ClinPred
0.99
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.99
gMVP
0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765364110; hg19: chr1-8925349; API