chr10-116874122-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001242699.2(ENO4):c.1262C>T(p.Ala421Val) variant causes a missense change. The variant allele was found at a frequency of 0.00002 in 1,549,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
ENO4
NM_001242699.2 missense
NM_001242699.2 missense
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 4.55
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]
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ACMG classification
Classification made for transcript
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=0.09051037).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENO4 | NM_001242699.2 | c.1262C>T | p.Ala421Val | missense_variant | 10/14 | ENST00000341276.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENO4 | ENST00000341276.11 | c.1262C>T | p.Ala421Val | missense_variant | 10/14 | 5 | NM_001242699.2 | P1 | |
ENO4 | ENST00000409522.5 | c.391-1943C>T | intron_variant | 1 | |||||
ENO4 | ENST00000369207.3 | c.734C>T | p.Ala245Val | missense_variant | 7/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152084Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000531 AC: 8AN: 150750Hom.: 0 AF XY: 0.0000495 AC XY: 4AN XY: 80820
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GnomAD4 exome AF: 0.0000186 AC: 26AN: 1397220Hom.: 0 Cov.: 30 AF XY: 0.0000174 AC XY: 12AN XY: 689112
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74414
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2023 | The c.1262C>T (p.A421V) alteration is located in exon 10 (coding exon 10) of the ENO4 gene. This alteration results from a C to T substitution at nucleotide position 1262, causing the alanine (A) at amino acid position 421 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
REVEL
Benign
Sift4G
Uncertain
T;T;T
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at