dbSNP rs1256511296: EIF5A:p.Asp128Asn (chr17-7311461-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_001970.5(EIF5A):c.382G>A(p.Asp128Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EIF5A
NM_001970.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.33

Publications

0 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 links:

GPS2 (HGNC:4550): (G protein pathway suppressor 2) This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]

GPS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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: 4.4819 (above the threshold of 3.09). GenCC associations: The gene is linked to Faundes-Banka syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.27446514).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001970.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF5A	NM_001970.5	MANE Select	c.382G>A	p.Asp128Asn	missense	Exon 4 of 6	NP_001961.1	P63241-1
EIF5A	NM_001143760.1		c.472G>A	p.Asp158Asn	missense	Exon 4 of 6	NP_001137232.1	P63241-2
EIF5A	NM_001143761.1		c.382G>A	p.Asp128Asn	missense	Exon 4 of 6	NP_001137233.1	P63241-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF5A	ENST00000336458.13	TSL:1 MANE Select	c.382G>A	p.Asp128Asn	missense	Exon 4 of 6	ENSP00000336776.8	P63241-1
EIF5A	ENST00000336452.11	TSL:1	c.472G>A	p.Asp158Asn	missense	Exon 4 of 6	ENSP00000336702.7	P63241-2
EIF5A	ENST00000416016.2	TSL:1	c.382G>A	p.Asp128Asn	missense	Exon 4 of 6	ENSP00000396073.2	P63241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251490

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.095

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.065

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

M_CAP

Benign

0.0031

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

7.3

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.064

Sift

Benign

0.19

Sift4G

Benign

0.29

Polyphen

0.0060

Vest4

0.15

MutPred

0.35

Gain of methylation at K126 (P = 0.0686)

MVP

0.49

MPC

1.7

ClinPred

0.92

GERP RS

4.5

Varity_R

0.50

gMVP

0.57

Mutation Taster

=61/39

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over