Variant 17-7309759-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3PP5_Moderate

The NM_001970.5(EIF5A):c.124G>A(p.Glu42Lys) 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 Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EIF5A
NM_001970.5 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.54

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 8 ACMG points.

PM1

In a region_of_interest Interaction with DOHH (size 70) in uniprot entity IF5A1_HUMAN there are 5 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, 0.776

PP5

Variant 17-7309759-G-A is Pathogenic according to our data. Variant chr17-7309759-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1695672.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF5A	NM_001970.5 linkuse as main transcript	c.124G>A	p.Glu42Lys	missense_variant	2/6	ENST00000336458.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF5A	ENST00000336458.13 linkuse as main transcript	c.124G>A	p.Glu42Lys	missense_variant	2/6	1	NM_001970.5	P1	P63241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Sep 20, 2024

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

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

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.042

MetaRNN

Pathogenic

0.78

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

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.6

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

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.4

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

REVEL

Uncertain

0.47

Sift

Benign

0.042

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

Sift4G

Benign

0.068

T;T;T;T;T;T;T;T;T

Polyphen

0.099

B;B;B;.;B;B;B;.;B

Vest4

0.66

MutPred

0.56

.;Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);

MVP

0.91

MPC

2.0

ClinPred

0.98

GERP RS

4.4

Varity_R

0.94

gMVP

0.94

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