Genetic Variant EIF5:p.Pro191Ser (chr14-103338458-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001969.5(EIF5):c.571C>T(p.Pro191Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000134 in 1,571,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

EIF5
NM_001969.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2348918).

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.571C>T	p.Pro191Ser	missense	Exon 7 of 12	NP_001960.2
	EIF5	NM_183004.5		c.571C>T	p.Pro191Ser	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.571C>T	p.Pro191Ser	missense	Exon 7 of 12	ENSP00000216554.3	P55010
EIF5	ENST00000392715.6	TSL:1	c.571C>T	p.Pro191Ser	missense	Exon 6 of 11	ENSP00000376477.2	P55010
EIF5	ENST00000558506.1	TSL:1	c.571C>T	p.Pro191Ser	missense	Exon 5 of 10	ENSP00000453743.1	P55010

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000224

AC:

AN:

178912

AF XY:

0.0000104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000807

Gnomad FIN exome

AF:

0.0000564

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1419752

Hom.:

Cov.:

AF XY:

0.00000853

AC XY:

AN XY:

703060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31862

American (AMR)

AF:

0.0000266

AC:

AN:

37618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25510

East Asian (EAS)

AF:

0.0000547

AC:

AN:

36592

South Asian (SAS)

AF:

0.00

AC:

AN:

82544

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

1089854

Other (OTH)

AF:

0.00

AC:

AN:

58870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

AF:

0.0000394

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000577

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000171

AC:

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

0.087

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Benign

0.12

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.1

PhyloP100

4.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.15

REVEL

Uncertain

0.37

Sift

Benign

0.22

Sift4G

Benign

0.66

Polyphen

0.73

Vest4

0.36

MVP

0.58

ClinPred

0.12

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.17

Mutation Taster

=65/35

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over