Variant 8-143579812-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130053.5(EEF1D):c.1924G>A(p.Ala642Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000092 in 1,565,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

EEF1D
NM_001130053.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

EEF1D (HGNC:3211): (eukaryotic translation elongation factor 1 delta) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.[provided by RefSeq, Aug 2010]

EEF1D links:

ENSG00000254741 (HGNC:):

ENSG00000254741 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1D	NM_001130053.5 link	c.1924G>A	p.Ala642Thr	missense_variant	Exon 10 of 10	ENST00000618139.4	NP_001123525.3	P29692-2D3DWK1B2RAR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1D	ENST00000618139.4 link	c.1924G>A	p.Ala642Thr	missense_variant	Exon 10 of 10	5	NM_001130053.5	ENSP00000484536.2		P29692-2A0A087X1X7

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000152

AC:

AN:

217514

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

116436

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.0000836

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.0000799

AC:

113

AN:

1413636

Hom.:

Cov.:

AF XY:

0.0000917

AC XY:

AN XY:

697560

show subpopulations

Gnomad4 AFR exome

AF:

0.0000623

Gnomad4 AMR exome

AF:

0.000444

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0000376

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000783

Gnomad4 OTH exome

AF:

0.0000687

GnomAD4 genome

AF:

0.000204

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1924G>A (p.A642T) alteration is located in exon 10 (coding exon 8) of the EEF1D gene. This alteration results from a G to A substitution at nucleotide position 1924, causing the alanine (A) at amino acid position 642 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T;.;T;T;.;.;.;T;T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

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

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.53

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

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.5

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

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.4

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

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.0020

D;D;D;T;D;D;D;D;D;D;D;D

Polyphen

1.0

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

Vest4

0.61

MVP

0.80

MPC

0.56

ClinPred

0.47

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.72

gMVP

0.42

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over