Genetic Variant EIF5:p.Pro190Thr (chr14-103338455-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001969.5(EIF5):c.568C>A(p.Pro190Thr) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF5
NM_001969.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

Publications

0 publications found

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]

EIF5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1918998).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001969.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF5	NM_001969.5	MANE Select	c.568C>A	p.Pro190Thr	missense	Exon 7 of 12	NP_001960.2
	EIF5	NM_183004.5		c.568C>A	p.Pro190Thr	missense	Exon 6 of 11	NP_892116.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF5	ENST00000216554.8	TSL:1 MANE Select	c.568C>A	p.Pro190Thr	missense	Exon 7 of 12	ENSP00000216554.3	P55010
EIF5	ENST00000392715.6	TSL:1	c.568C>A	p.Pro190Thr	missense	Exon 6 of 11	ENSP00000376477.2	P55010
EIF5	ENST00000558506.1	TSL:1	c.568C>A	p.Pro190Thr	missense	Exon 5 of 10	ENSP00000453743.1	P55010

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.03e-7

AC:

AN:

1422798

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31926

American (AMR)

AF:

0.00

AC:

AN:

38030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25562

East Asian (EAS)

AF:

0.00

AC:

AN:

36782

South Asian (SAS)

AF:

0.00

AC:

AN:

82836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091522

Other (OTH)

AF:

0.00

AC:

AN:

58984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

0.0054

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.045

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

M_CAP

Benign

0.031

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.2

PhyloP100

2.9

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.39

REVEL

Benign

0.26

Sift

Benign

0.47

Sift4G

Benign

0.58

Polyphen

0.26

Vest4

0.37

MutPred

0.25

Gain of phosphorylation at P190 (P = 0.0023)

MVP

0.52

ClinPred

0.43

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.19

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over