Genetic Variant EIF5A:p.Arg13Gly (chr17-7307083-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_001143760.1(EIF5A):c.37C>G(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,603,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

EIF5A
NM_001143760.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a chain Eukaryotic translation initiation factor 5A-1 (size 152) in uniprot entity IF5A1_HUMAN there are 16 pathogenic changes around while only 1 benign (94%) in NM_001143760.1

BP4

Computational evidence support a benign effect (MetaRNN=0.032257974).

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
EIF5A	NM_001143760.1 link	c.37C>G	p.Arg13Gly	missense_variant	Exon 1 of 6	NP_001137232.1	P63241-2
EIF5A	NM_001370420.1 link	c.-52C>G		5_prime_UTR_variant	Exon 1 of 6	NP_001357349.1
EIF5A	XM_017024301.3 link	c.-59C>G		5_prime_UTR_variant	Exon 1 of 2	XP_016879790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF5A	ENST00000336452.11 link	c.37C>G	p.Arg13Gly	missense_variant	Exon 1 of 6	1		ENSP00000336702.7		P63241-2
EIF5A	ENST00000355068.4 link	n.-243C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152226

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:

0.00

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:

0.00000423

AC:

AN:

236214

Hom.:

AF XY:

0.00000779

AC XY:

AN XY:

128394

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:

0.00000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1451180

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

720994

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:

0.0000154

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.28

M_CAP

Benign

0.0018

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.14

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.089

MutPred

0.16

Loss of MoRF binding (P = 0.0168);

MVP

0.16

MPC

0.0017

ClinPred

0.020

GERP RS

0.67

gMVP

0.31

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over