Variant 10-116856586-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242699.2(ENO4):c.389C>T(p.Ala130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,383,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14513654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO4	NM_001242699.2 link	c.389C>T	p.Ala130Val	missense_variant	3/14	ENST00000341276.11	NP_001229628.1	A6NNW6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ENO4	ENST00000341276.11 link	c.389C>T	p.Ala130Val	missense_variant	3/14	5	NM_001242699.2	ENSP00000345555.6	A6NNW6-3
ENO4	ENST00000409522.5 link	c.165+6855C>T		intron_variant		1		ENSP00000387194.1	A6NNW6-2
ENO4	ENST00000622726.4 link	c.392C>T	p.Ala131Val	missense_variant	4/16	5			A0A5H1ZRS3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000730

AC:

AN:

137044

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74512

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:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1383838

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

682860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000352

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000416

AC:

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

Aug 14, 2024

The c.389C>T (p.A130V) alteration is located in exon 3 (coding exon 3) of the ENO4 gene. This alteration results from a C to T substitution at nucleotide position 389, causing the alanine (A) at amino acid position 130 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.0060

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.87

D;.

M_CAP

Benign

0.0098

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.40

REVEL

Benign

0.12

Sift4G

Uncertain

0.014

D;D

Vest4

0.23

MVP

0.040

ClinPred

0.71

GERP RS

4.0

Varity_R

0.054

gMVP

0.54

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

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