Variant 15-39973598-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_001013703.4(EIF2AK4):c.1667A>T(p.Glu556Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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. E556G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF2AK4
NM_001013703.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

EIF2AK4 (HGNC:19687): (eukaryotic translation initiation factor 2 alpha kinase 4) This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

EIF2AK4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant where missense usually causes diseases, EIF2AK4

BP4

Computational evidence support a benign effect (MetaRNN=0.104720026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK4	NM_001013703.4 linkuse as main transcript	c.1667A>T	p.Glu556Val	missense_variant	11/39	ENST00000263791.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK4	ENST00000263791.10 linkuse as main transcript	c.1667A>T	p.Glu556Val	missense_variant	11/39	2	NM_001013703.4	P1	Q9P2K8-1
EIF2AK4	ENST00000559624.5 linkuse as main transcript	c.1667A>T	p.Glu556Val	missense_variant	11/11	1			Q9P2K8-3
EIF2AK4	ENST00000560855.5 linkuse as main transcript	c.1085A>T	p.Glu362Val	missense_variant	7/34	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152138

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1457726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725064

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;N

Sift

Benign

0.21

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0

B;B

Vest4

0.079

MutPred

0.29

Loss of disorder (P = 0.0399);Loss of disorder (P = 0.0399);

MVP

0.82

MPC

1.2

ClinPred

0.26

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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