10-116860901-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001242699.2(ENO4):c.742G>C(p.Ala248Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: -0.156

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENO4	NM_001242699.2	c.742G>C	p.Ala248Pro	missense_variant	5/14	ENST00000341276.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENO4	ENST00000341276.11	c.742G>C	p.Ala248Pro	missense_variant	5/14	5	NM_001242699.2	P1
ENO4	ENST00000409522.5	c.166-7749G>C		intron_variant		1
ENO4	ENST00000369207.3	c.214G>C	p.Ala72Pro	missense_variant	2/11	5

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.742G>C (p.A248P) alteration is located in exon 5 (coding exon 5) of the ENO4 gene. This alteration results from a G to C substitution at nucleotide position 742, causing the alanine (A) at amino acid position 248 to be replaced by a proline (P). 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	0.78
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	17
Dann	Uncertain	0.99
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.86	D;.;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.32	T
REVEL	Uncertain	0.52
Sift4G	Uncertain	0.040	D;D;D
Vest4		0.51
MVP		0.30
ClinPred		0.35	T
GERP RS		-0.59
Varity_R		0.16
gMVP		0.90

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: chr10-118620412;