NM_001242699.2:c.716G>A

Variant names:

• chr10-116860875-G-A
• NM_001242699.2:c.716G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001242699.2(ENO4):​c.716G>A​(p.Gly239Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO4	NM_001242699.2	c.716G>A	p.Gly239Glu	missense_variant	Exon 5 of 14	ENST00000341276.11	NP_001229628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO4	ENST00000341276.11	c.716G>A	p.Gly239Glu	missense_variant	Exon 5 of 14	5	NM_001242699.2	ENSP00000345555.6
ENO4	ENST00000409522.5	c.166-7775G>A		intron_variant	Intron 1 of 6	1		ENSP00000387194.1
ENO4	ENST00000622726.4	c.719G>A	p.Gly240Glu	missense_variant	Exon 6 of 16	5
ENO4	ENST00000369207.3	c.185G>A	p.Gly62Glu	missense_variant	Exon 2 of 11	5		ENSP00000358208.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.716G>A (p.G239E) alteration is located in exon 5 (coding exon 5) of the ENO4 gene. This alteration results from a G to A substitution at nucleotide position 716, causing the glycine (G) at amino acid position 239 to be replaced by a glutamic acid (E). 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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;.;D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.29	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	.;.;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.022	.;.;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.80
MVP		0.43
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.50
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-118620386;