10-116849718-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001242699.2(ENO4):c.152T>C(p.Val51Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,370,444 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: 7.3e-7 (0 hom.)
• Consequence: ENO4 NM_001242699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28684127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENO4	NM_001242699.2	c.152T>C	p.Val51Ala	missense_variant	1/14	ENST00000341276.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENO4	ENST00000341276.11	c.152T>C	p.Val51Ala	missense_variant	1/14	5	NM_001242699.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370444 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 673594

Gnomad4 AFR exome AF: 0.00

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: 9.39e-7

Gnomad4 OTH exome AF: 0.00

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

Jun 28, 2023

The c.152T>C (p.V51A) alteration is located in exon 1 (coding exon 1) of the ENO4 gene. This alteration results from a T to C substitution at nucleotide position 152, causing the valine (V) at amino acid position 51 to be replaced by an alanine (A). 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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
Cadd	Pathogenic	29
Dann	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	T;T;.
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L;L;.
MutationTaster	Benign	0.79	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.68	N;N;.
REVEL	Benign	0.27
Sift	Uncertain	0.014	D;D;.
Sift4G	Benign	0.32	T;D;D
Polyphen		0.88	P;.;.
Vest4		0.24
MutPred		0.49		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.35
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.41

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: chr10-118609229;