chr14-103338408-C-T

Variant summary

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

The NM_001969.5(EIF5):​c.521C>T​(p.Ser174Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,606,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EIF5
NM_001969.5 missense

Scores

15
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
Variant links:
Genes affected
EIF5 (HGNC:3299): (eukaryotic translation initiation factor 5) Eukaryotic translation initiation factor-5 (EIF5) interacts with the 40S initiation complex to promote hydrolysis of bound GTP with concomitant joining of the 60S ribosomal subunit to the 40S initiation complex. The resulting functional 80S ribosomal initiation complex is then active in peptidyl transfer and chain elongations (summary by Si et al., 1996 [PubMed 8663286]).[supplied by OMIM, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF5NM_001969.5 linkc.521C>T p.Ser174Phe missense_variant Exon 7 of 12 ENST00000216554.8 NP_001960.2 P55010A0A024R6Q1
EIF5NM_183004.5 linkc.521C>T p.Ser174Phe missense_variant Exon 6 of 11 NP_892116.2 P55010A0A024R6Q1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF5ENST00000216554.8 linkc.521C>T p.Ser174Phe missense_variant Exon 7 of 12 1 NM_001969.5 ENSP00000216554.3 P55010

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152058
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000433
AC:
1
AN:
231196
Hom.:
0
AF XY:
0.00000796
AC XY:
1
AN XY:
125608
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000996
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1454842
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
723404
show subpopulations
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152058
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.521C>T (p.S174F) alteration is located in exon 7 (coding exon 5) of the EIF5 gene. This alteration results from a C to T substitution at nucleotide position 521, causing the serine (S) at amino acid position 174 to be replaced by a phenylalanine (F). 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
0.18
BayesDel_addAF
Uncertain
0.089
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.89
.;D;.;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.62
D;D;D;D
MetaSVM
Uncertain
0.041
D
MutationAssessor
Uncertain
2.0
M;.;M;M
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.9
D;D;D;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0080
D;D;D;D
Sift4G
Uncertain
0.016
D;D;D;D
Polyphen
0.90
P;.;P;P
Vest4
0.48
MVP
0.69
ClinPred
0.75
D
GERP RS
5.0
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.30
gMVP
0.27

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: rs1480636875; hg19: chr14-103804745; API