Variant 17-7309778-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_ModeratePM1PM2PP2PP3PP5

The NM_001970.5(EIF5A):c.143C>A(p.Thr48Asn) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

EIF5A
NM_001970.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.39

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_pathogenic. Variant got 9 ACMG points.

PS1

Transcript NM_001970.5 (EIF5A) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM1

In a chain Eukaryotic translation initiation factor 5A-1 (size 152) in uniprot entity IF5A1_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_001970.5

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EIF5A. . Gene score misZ 2.407 (greater than the threshold 3.09). Trascript score misZ 4.4819 (greater than threshold 3.09). GenCC has associacion of gene with Faundes-Banka syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

PP5

Variant 17-7309778-C-A is Pathogenic according to our data. Variant chr17-7309778-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 1164078.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-7309778-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF5A	NM_001970.5 linkuse as main transcript	c.143C>A	p.Thr48Asn	missense_variant	2/6	ENST00000336458.13	NP_001961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF5A	ENST00000336458.13 linkuse as main transcript	c.143C>A	p.Thr48Asn	missense_variant	2/6	1	NM_001970.5	ENSP00000336776	P1	P63241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Faundes-Banka syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

.;D;D;.;D;D;D;T;D

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;.;.;D;.;.;.;D;D

M_CAP

Benign

0.058

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.059

MutationAssessor

Pathogenic

3.5

.;M;M;.;M;M;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PROVEAN

Pathogenic

-4.7

D;D;.;.;.;D;.;.;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D;.;.;.;D;.;.;D

Sift4G

Uncertain

0.030

D;D;D;D;D;D;D;D;D

Polyphen

0.98

D;P;P;.;P;P;P;.;P

Vest4

0.68

MutPred

0.52

.;Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);Loss of phosphorylation at T48 (P = 0.0433);

MVP

0.73

MPC

3.0

ClinPred

1.0

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.93

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over