Genetic Variant ENO1:p.Asp266Glu (chr1-8865352-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001428.5(ENO1):c.798C>A(p.Asp266Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D266G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ENO1
NM_001428.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.822

Publications

0 publications found

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]

ENO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23382655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001428.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENO1	NM_001428.5	MANE Select	c.798C>A	p.Asp266Glu	missense	Exon 8 of 12	NP_001419.1	P06733-1
ENO1	NM_001353346.3		c.798C>A	p.Asp266Glu	missense	Exon 8 of 12	NP_001340275.1	A0A2R8Y6G6
ENO1	NM_001201483.4		c.519C>A	p.Asp173Glu	missense	Exon 7 of 11	NP_001188412.1	P06733-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENO1	ENST00000234590.10	TSL:1 MANE Select	c.798C>A	p.Asp266Glu	missense	Exon 8 of 12	ENSP00000234590.4	P06733-1
ENO1	ENST00000464920.2	TSL:1	n.1683C>A		non_coding_transcript_exon	Exon 5 of 9
ENO1	ENST00000879697.1		c.828C>A	p.Asp276Glu	missense	Exon 8 of 12	ENSP00000549756.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.39

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.0087

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

PhyloP100

0.82

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Benign

0.11

Polyphen

0.0030

Vest4

0.56

MutPred

0.46

Gain of glycosylation at S268 (P = 0.141)

MVP

0.52

MPC

0.28

ClinPred

0.93

GERP RS

-5.4

Varity_R

0.88

gMVP

0.81

Mutation Taster

=43/57

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over