Variant 10-116859000-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.496G>A(p.Ala166Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000398 in 1,532,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 1 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

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=0.055704474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO4	NM_001242699.2 linkuse as main transcript	c.496G>A	p.Ala166Thr	missense_variant	4/14	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.496G>A	p.Ala166Thr	missense_variant	4/14	5	NM_001242699.2	ENSP00000345555	P1	A6NNW6-3
ENO4	ENST00000409522.5 linkuse as main transcript	c.165+9269G>A		intron_variant		1		ENSP00000387194		A6NNW6-2
ENO4	ENST00000369207.3 linkuse as main transcript			upstream_gene_variant		5		ENSP00000358208

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000294

AC:

AN:

136160

Hom.:

AF XY:

0.0000135

AC XY:

AN XY:

74030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000289

Gnomad NFE exome

AF:

0.0000374

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000413

AC:

AN:

1380910

Hom.:

Cov.:

AF XY:

0.0000514

AC XY:

AN XY:

681526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000634

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000887

Gnomad4 NFE exome

AF:

0.0000214

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000727

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000897

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

Jul 20, 2021

The c.496G>A (p.A166T) alteration is located in exon 4 (coding exon 4) of the ENO4 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the alanine (A) at amino acid position 166 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.92

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.64

T;.

M_CAP

Benign

0.0071

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.30

REVEL

Benign

0.11

Sift4G

Benign

0.42

T;T

Vest4

0.12

MVP

0.061

ClinPred

0.19

GERP RS

5.3

Varity_R

0.10

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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