17-4955567-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_053013.4(ENO3):​c.828C>T​(p.Leu276Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,614,210 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: ENO3 NM_053013.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-4955567-C-T is Benign according to our data. Variant chr17-4955567-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 471071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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>T	p.Leu276Leu	synonymous	Exon 8 of 12	NP_443739.3	P13929-1
	ENO3	NM_001374524.1		c.855C>T	p.Leu285Leu	synonymous	Exon 8 of 12	NP_001361453.1
	ENO3	NM_001374523.1		c.828C>T	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>T	p.Leu276Leu	synonymous	Exon 8 of 12	ENSP00000430055.2	P13929-1
	ENO3	ENST00000518175.1	TSL:1	c.828C>T	p.Leu276Leu	synonymous	Exon 7 of 11	ENSP00000431087.1	P13929-1
	ENO3	ENST00000521659.5	TSL:1	n.*774C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000430554.1	E5RJH5

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 267 AN: 152208 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000529 AC: 133 AN: 251462 AF XY: 0.000331

Gnomad AFR exome AF: 0.00701

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000169 AC: 247 AN: 1461884 Hom.: 1 Cov.: 33 AF XY: 0.000138 AC XY: 100 AN XY: 727240

African (AFR) AF: 0.00568 AC: 190 AN: 33480

American (AMR) AF: 0.000537 AC: 24 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112008

Other (OTH) AF: 0.000281 AC: 17 AN: 60396

GnomAD4 genome AF: 0.00175 AC: 266 AN: 152326 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74480

African (AFR) AF: 0.00616 AC: 256 AN: 41570

American (AMR) AF: 0.000588 AC: 9 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000830 Hom.: 0

Bravo AF: 0.00195

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ENO3-related disorder (1)
-	-	1	Glycogen storage disease due to muscle beta-enolase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.95
DANN	Benign	0.86
PhyloP100		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism

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: COSV104568006; COSMIC: COSV104568006;