17-7311104-C-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001970.5(EIF5A):c.252C>G(p.Ile84Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
EIF5A
NM_001970.5 missense
NM_001970.5 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 1.96
Genes affected
EIF5A (HGNC:3300): (eukaryotic translation initiation factor 5A) Enables U6 snRNA binding activity and protein N-terminus binding activity. Involved in several processes, including cellular response to virus; positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; and tumor necrosis factor-mediated signaling pathway. Located in annulate lamellae; cytoplasm; and nucleus. Part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a chain Eukaryotic translation initiation factor 5A-1 (size 152) in uniprot entity IF5A1_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_001970.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.858
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 01, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;T;T;.;T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;D;.;.;.;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;.;M;M;M;.;M
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.;.;.;N;.;.;N
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.;.;D;.;.;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
P;P;P;.;P;P;P;.;P
Vest4
MutPred
0.83
.;Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);Loss of methylation at K85 (P = 0.0272);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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
Publications
No publications associated with this variant yet.