1-8863250-CCC-GCG

Variant names:

• chr1-8863250-CCC-GCG
• NM_001428.5:c.1159_1161delGGGinsCGC
• ENO1 p.Gly387Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001428.5(ENO1):​c.1159_1161delGGGinsCGC​(p.Gly387Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: 7.79
• Publications: 0 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO1	NM_001428.5	MANE Select	c.1159_1161delGGGinsCGC	p.Gly387Arg	missense	N/A	NP_001419.1	P06733-1
	ENO1	NM_001353346.3		c.1159_1161delGGGinsCGC	p.Gly387Arg	missense	N/A	NP_001340275.1	A0A2R8Y6G6
	ENO1	NM_001201483.4		c.880_882delGGGinsCGC	p.Gly294Arg	missense	N/A	NP_001188412.1	P06733-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO1	ENST00000234590.10	TSL:1 MANE Select	c.1159_1161delGGGinsCGC	p.Gly387Arg	missense	N/A	ENSP00000234590.4	P06733-1
	ENO1	ENST00000464920.2	TSL:1	n.2044_2046delGGGinsCGC		non_coding_transcript_exon	Exon 7 of 9
	ENO1	ENST00000879697.1		c.1189_1191delGGGinsCGC	p.Gly397Arg	missense	N/A	ENSP00000549756.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-8923309;