Variant 10-116849678-G-A 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.112G>A(p.Glu38Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000716 in 1,397,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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:

HSPA12A (HGNC:19022): (heat shock protein family A (Hsp70) member 12A) Predicted to enable ATP binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

HSPA12A links:

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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=0.20154852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENO4	NM_001242699.2 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	1/14	ENST00000341276.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENO4	ENST00000341276.11 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	1/14	5	NM_001242699.2	P1	A6NNW6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000687

AC:

AN:

145516

Hom.:

AF XY:

0.00

AC XY:

AN XY:

78470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000410

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1397314

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 31, 2022

The c.112G>A (p.E38K) alteration is located in exon 1 (coding exon 1) of the ENO4 gene. This alteration results from a G to A substitution at nucleotide position 112, causing the glutamic acid (E) at amino acid position 38 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

0.20

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.90

D;D;.

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.13

N;N;.

REVEL

Benign

0.094

Sift

Benign

0.11

T;D;.

Sift4G

Benign

0.78

T;D;D

Polyphen

0.73

P;.;.

Vest4

0.36

MutPred

0.35

Gain of methylation at E38 (P = 0.0186);Gain of methylation at E38 (P = 0.0186);Gain of methylation at E38 (P = 0.0186);

MVP

0.30

ClinPred

0.52

GERP RS

3.9

Varity_R

0.16

gMVP

0.51

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