rs11544514

Variant names:

• chr1-8863984-G-T
• rs11544514
• NM_001428.5:c.974C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001428.5(ENO1):​c.974C>A​(p.Pro325Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENO1 NM_001428.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.84
• Publications: 7 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO1	NM_001428.5	c.974C>A	p.Pro325Gln	missense_variant	Exon 9 of 12	ENST00000234590.10	NP_001419.1
ENO1	NM_001353346.3	c.974C>A	p.Pro325Gln	missense_variant	Exon 9 of 12		NP_001340275.1
ENO1	NM_001201483.4	c.695C>A	p.Pro232Gln	missense_variant	Exon 8 of 11		NP_001188412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO1	ENST00000234590.10	c.974C>A	p.Pro325Gln	missense_variant	Exon 9 of 12	1	NM_001428.5	ENSP00000234590.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;D;.
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	4.3	H;H;.
PhyloP100		9.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.4	D;.;.
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.0030	D;.;.
Polyphen		1.0	D;D;.
Vest4		0.85
MutPred		0.25		Gain of ubiquitination at K326 (P = 0.0825);Gain of ubiquitination at K326 (P = 0.0825);Gain of ubiquitination at K326 (P = 0.0825);
MVP		0.89
MPC		0.96
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.82
Mutation Taster		=21/79	disease causing

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

Other links and lift over

dbSNP: rs11544514; hg19: chr1-8924043;