rs11544491

Variant names:

• chr1-8868016-C-A
• rs11544491
• NM_001428.5:c.282G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-8868016-C-A
• chr1-8868016-C-G
• chr1-8868016-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001201483.4(ENO1):​c.3G>T​(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENO1 NM_001201483.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 1 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.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 4 codons. Genomic position: 8868009. Lost 0.010 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201483.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO1	NM_001428.5	MANE Select	c.282G>T	p.Met94Ile	missense	Exon 5 of 12	NP_001419.1	P06733-1
	ENO1	NM_001201483.4		c.3G>T	p.Met1?	start_lost	Exon 4 of 11	NP_001188412.1	P06733-2
	ENO1	NM_001353346.3		c.282G>T	p.Met94Ile	missense	Exon 5 of 12	NP_001340275.1	A0A2R8Y6G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO1	ENST00000234590.10	TSL:1 MANE Select	c.282G>T	p.Met94Ile	missense	Exon 5 of 12	ENSP00000234590.4	P06733-1
	ENO1	ENST00000464920.2	TSL:1	n.1167G>T		non_coding_transcript_exon	Exon 2 of 9
	ENO1	ENST00000879697.1		c.282G>T	p.Met94Ile	missense	Exon 5 of 12	ENSP00000549756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.025	D
Polyphen		0.84	P
Vest4		0.86
MutPred		0.48		Loss of ubiquitination at K89 (P = 0.0532)
MVP		0.87
MPC		0.34
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.63
gMVP		0.81
Mutation Taster		=5/95	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: rs11544491; hg19: chr1-8928075;