Variant 10-116862805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001242699.2(ENO4):c.943G>A(p.Glu315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,549,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

ENO4 (HGNC:31670): (enolase 4) Predicted to enable phosphopyruvate hydratase activity. Predicted to be involved in glycolytic process and regulation of vacuole fusion, non-autophagic. Predicted to act upstream of or within cilium organization and flagellated sperm motility. Predicted to be located in sperm principal piece. Predicted to be part of phosphopyruvate hydratase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENO4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042934746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO4	NM_001242699.2 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	7/14	ENST00000341276.11	NP_001229628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENO4	ENST00000341276.11 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	7/14	5	NM_001242699.2	ENSP00000345555	P1	A6NNW6-3
ENO4	ENST00000409522.5 linkuse as main transcript	c.166-5845G>A		intron_variant		1		ENSP00000387194		A6NNW6-2
ENO4	ENST00000369207.3 linkuse as main transcript	c.415G>A	p.Glu139Lys	missense_variant	4/11	5		ENSP00000358208

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000288

AC:

AN:

149064

Hom.:

AF XY:

0.000386

AC XY:

AN XY:

80292

show subpopulations

Gnomad AFR exome

AF:

0.000148

Gnomad AMR exome

AF:

0.0000814

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00102

Gnomad SAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.000536

Gnomad NFE exome

AF:

0.000145

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

172

AN:

1397306

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

105

AN XY:

689248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00123

Gnomad4 SAS exome

AF:

0.000480

Gnomad4 FIN exome

AF:

0.000270

Gnomad4 NFE exome

AF:

0.0000557

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.000131

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000106

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000416

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2023

The c.943G>A (p.E315K) alteration is located in exon 7 (coding exon 7) of the ENO4 gene. This alteration results from a G to A substitution at nucleotide position 943, causing the glutamic acid (E) at amino acid position 315 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.82

T;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.78

D;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.080

.;.;N

REVEL

Benign

0.066

Sift

Benign

0.49

.;.;T

Sift4G

Benign

0.16

T;T;T

Vest4

0.30

MVP

0.14

ClinPred

0.016

GERP RS

3.4

Varity_R

0.037

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over