Genetic Variant ENST00000336452.11:c.37C>T (chr17-7307083-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The ENST00000336452.11(EIF5A):c.37C>T(p.Arg13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000904 in 1,603,524 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

EIF5A
ENST00000336452.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.158

Publications

2 publications found

Variant links:

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]

EIF5A Gene-Disease associations (from GenCC):

Faundes-Banka syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

EIF5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 2.407 (below the threshold of 3.09). Trascript score misZ: 3.6907 (above the threshold of 3.09). GenCC associations: The gene is linked to Faundes-Banka syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.008883923).

BS2

High AC in GnomAd4 at 82 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336452.11. 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
	EIF5A	NM_001143760.1		c.37C>T	p.Arg13Cys	missense	Exon 1 of 6	NP_001137232.1	P63241-2
	EIF5A	NM_001370420.1		c.-52C>T		5_prime_UTR	Exon 1 of 6	NP_001357349.1	P63241-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF5A	ENST00000336452.11	TSL:1	c.37C>T	p.Arg13Cys	missense	Exon 1 of 6	ENSP00000336702.7	P63241-2
EIF5A	ENST00000939950.1		c.-54C>T		5_prime_UTR	Exon 1 of 5	ENSP00000610009.1
EIF5A	ENST00000894295.1		c.-52C>T		5_prime_UTR	Exon 1 of 6	ENSP00000564354.1

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.0000889

AC:

AN:

236214

AF XY:

0.0000701

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000434

AC:

AN:

1451180

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

720994

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

33322

American (AMR)

AF:

0.000115

AC:

AN:

43386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39470

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1106870

Other (OTH)

AF:

0.000183

AC:

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

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:

0.000538

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41580

American (AMR)

AF:

0.000915

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000683

Hom.:

Bravo

AF:

0.000623

ExAC

AF:

0.0000997

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

0.22

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.48

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

PhyloP100

-0.16

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.42

REVEL

Benign

0.024

Sift

Uncertain

0.015

Sift4G

Uncertain

0.046

Polyphen

0.13

Vest4

0.20

MutPred

0.16

Loss of MoRF binding (P = 0.0047)

MVP

0.21

MPC

0.0017

ClinPred

0.030

GERP RS

0.67

PromoterAI

-0.0054

Neutral

(source)

gMVP

0.38

Splicing

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