10-116881569-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001242699.2(ENO4):​c.1778C>T​(p.Ala593Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,549,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.149
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]
SHTN1 (HGNC:29319): (shootin 1) Enables identical protein binding activity. Involved in positive regulation of neuron migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04776874).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENO4NM_001242699.2 linkc.1778C>T p.Ala593Val missense_variant Exon 14 of 14 ENST00000341276.11 NP_001229628.1 A6NNW6-3
SHTN1NM_001127211.3 linkc.*4775G>A 3_prime_UTR_variant Exon 17 of 17 ENST00000355371.9 NP_001120683.1 A0MZ66-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENO4ENST00000341276.11 linkc.1778C>T p.Ala593Val missense_variant Exon 14 of 14 5 NM_001242699.2 ENSP00000345555.6 A6NNW6-3
SHTN1ENST00000355371 linkc.*4775G>A 3_prime_UTR_variant Exon 17 of 17 2 NM_001127211.3 ENSP00000347532.4 A0MZ66-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152144
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000336
AC:
5
AN:
148792
Hom.:
0
AF XY:
0.0000374
AC XY:
3
AN XY:
80170
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000818
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:
0.0000546
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000451
AC:
63
AN:
1397768
Hom.:
0
Cov.:
30
AF XY:
0.0000363
AC XY:
25
AN XY:
689396
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000561
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:
0.0000565
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152144
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1778C>T (p.A593V) alteration is located in exon 14 (coding exon 14) of the ENO4 gene. This alteration results from a C to T substitution at nucleotide position 1778, causing the alanine (A) at amino acid position 593 to be replaced by a valine (V). 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
0.091
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
7.6
DANN
Benign
0.96
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.74
T;T;.
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.048
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.41
N;.;.
REVEL
Benign
0.056
Sift
Benign
0.34
T;.;.
Sift4G
Benign
0.11
T;T;T
Polyphen
0.028
B;.;.
Vest4
0.061
MVP
0.048
ClinPred
0.036
T
GERP RS
0.90
Varity_R
0.020
gMVP
0.17

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.

Other links and lift over

dbSNP: rs905832855; hg19: chr10-118641080; API