1-8865344-C-A

Position:

• chr1-8865344-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000234590.10(ENO1):​c.806G>T​(p.Arg269Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENO1 ENST00000234590.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO1	NM_001428.5	c.806G>T	p.Arg269Met	missense_variant	8/12	ENST00000234590.10	NP_001419.1
ENO1	NM_001353346.3	c.806G>T	p.Arg269Met	missense_variant	8/12		NP_001340275.1
ENO1	NM_001201483.4	c.527G>T	p.Arg176Met	missense_variant	7/11		NP_001188412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENO1	ENST00000234590.10	c.806G>T	p.Arg269Met	missense_variant	8/12	1	NM_001428.5	ENSP00000234590	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.806G>T (p.R269M) alteration is located in exon 8 (coding exon 7) of the ENO1 gene. This alteration results from a G to T substitution at nucleotide position 806, causing the arginine (R) at amino acid position 269 to be replaced by a methionine (M). 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	0.72
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.27	T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.3	M;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	D;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.014	D;.;.
Sift4G	Benign	0.082	T;.;.
Polyphen		0.50	P;P;.
Vest4		0.72
MutPred		0.32		Loss of catalytic residue at R269 (P = 0.0766);Loss of catalytic residue at R269 (P = 0.0766);Loss of catalytic residue at R269 (P = 0.0766);
MVP		0.90
MPC		0.64
ClinPred		0.98	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.53
gMVP		0.87

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: chr1-8925403;