17-4955082-A-T

Variant names:

• chr17-4955082-A-T
• rs560867570
• NM_053013.4:c.452A>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_053013.4(ENO3):​c.452A>T​(p.Asn151Ile) 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ENO3 NM_053013.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO3	NM_053013.4	c.452A>T	p.Asn151Ile	missense_variant	Exon 7 of 12	ENST00000519602.6	NP_443739.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO3	ENST00000519602.6	c.452A>T	p.Asn151Ile	missense_variant	Exon 7 of 12	2	NM_053013.4	ENSP00000430055.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74282

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	.;T;.;D;.;.;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;.;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	4.9	.;.;.;H;.;.;H
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.0	.;.;D;D;D;D;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	.;.;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		0.95	.;.;.;.;.;P;.
Vest4		0.97, 0.96, 0.97
MutPred		0.88		Loss of catalytic residue at N151 (P = 0.032);Loss of catalytic residue at N151 (P = 0.032);Loss of catalytic residue at N151 (P = 0.032);Loss of catalytic residue at N151 (P = 0.032);Loss of catalytic residue at N151 (P = 0.032);.;Loss of catalytic residue at N151 (P = 0.032);
MVP		0.88
MPC		0.48
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.98
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs560867570; hg19: chr17-4858377;