rs35119507

Variant names:

• chr17-4955567-C-A
• rs35119507
• NM_053013.4:c.828C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-4955567-C-A
• chr17-4955567-C-G
• chr17-4955567-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_053013.4(ENO3):​c.828C>A​(p.Leu276Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L276L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENO3 NM_053013.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897
• Publications: 1 publications found

Genes affected

ENO3 (HGNC:3354): (enolase 3) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme is found in skeletal muscle cells in the adult where it may play a role in muscle development and regeneration. A switch from alpha enolase to beta enolase occurs in muscle tissue during development in rodents. Mutations in this gene have be associated glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jul 2010]

ENO3 Gene-Disease associations (from GenCC):

• glycogen storage disease due to muscle beta-enolase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.897 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053013.4. 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
	ENO3	NM_053013.4	MANE Select	c.828C>A	p.Leu276Leu	synonymous	Exon 8 of 12	NP_443739.3	P13929-1
	ENO3	NM_001374524.1		c.855C>A	p.Leu285Leu	synonymous	Exon 8 of 12	NP_001361453.1
	ENO3	NM_001374523.1		c.828C>A	p.Leu276Leu	synonymous	Exon 8 of 12	NP_001361452.1	P13929-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO3	ENST00000519602.6	TSL:2 MANE Select	c.828C>A	p.Leu276Leu	synonymous	Exon 8 of 12	ENSP00000430055.2	P13929-1
	ENO3	ENST00000518175.1	TSL:1	c.828C>A	p.Leu276Leu	synonymous	Exon 7 of 11	ENSP00000431087.1	P13929-1
	ENO3	ENST00000521659.5	TSL:1	n.*774C>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000430554.1	E5RJH5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.20
DANN	Benign	0.80
PhyloP100		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35119507; hg19: chr17-4858862; COSMIC: COSV52777024; COSMIC: COSV52777024;