10-116860844-G-C

Variant names:

• chr10-116860844-G-C
• rs551253938
• NM_001242699.2:c.685G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242699.2(ENO4):​c.685G>C​(p.Glu229Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000359 in 1,394,294 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: 0.0000036 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2339468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO4	NM_001242699.2	c.685G>C	p.Glu229Gln	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.685G>C	p.Glu229Gln	missense_variant	Exon 5 of 14	5	NM_001242699.2	ENSP00000345555.6
ENO4	ENST00000409522.5	c.166-7806G>C		intron_variant	Intron 1 of 6	1		ENSP00000387194.1
ENO4	ENST00000622726.4	c.688G>C	p.Glu230Gln	missense_variant	Exon 6 of 16	5
ENO4	ENST00000369207.3	c.154G>C	p.Glu52Gln	missense_variant	Exon 2 of 11	5		ENSP00000358208.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000359 AC: 5 AN: 1394294 Hom.: 0 Cov.: 30 AF XY: 0.00000436 AC XY: 3 AN XY: 687430

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

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: 9.29e-7

Gnomad4 OTH exome AF: 0.0000346

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.685G>C (p.E229Q) 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 685, causing the glutamic acid (E) at amino acid position 229 to be replaced by a glutamine (Q). 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	0.17
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;.
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.34	T
PrimateAI	Benign	0.44	T
REVEL	Benign	0.22
Sift4G	Uncertain	0.034	D;D
Vest4		0.11
MVP		0.085
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.64

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

Other links and lift over

dbSNP: rs551253938; hg19: chr10-118620355;