Variant 8-143581088-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130053.5(EEF1D):c.1454C>T(p.Ser485Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,612,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

EEF1D
NM_001130053.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13931286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1D	NM_001130053.5 linkuse as main transcript	c.1454C>T	p.Ser485Leu	missense_variant	7/10	ENST00000618139.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1D	ENST00000618139.4 linkuse as main transcript	c.1454C>T	p.Ser485Leu	missense_variant	7/10	5	NM_001130053.5		P29692-2
	ENST00000623257.1 linkuse as main transcript	n.2731G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000440

AC:

AN:

250120

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1460152

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726400

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2022

The c.1454C>T (p.S485L) alteration is located in exon 7 (coding exon 5) of the EEF1D gene. This alteration results from a C to T substitution at nucleotide position 1454, causing the serine (S) at amino acid position 485 to be replaced by a leucine (L). 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

Benign

0.067

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

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

Eigen

Benign

0.051

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

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

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

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

MutationTaster

Benign

0.94

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

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.5

D;D;N;N;N;N;N;D;D;N;N;.;D;N;D;D;N;D;D;N;D

REVEL

Benign

0.19

Sift

Benign

0.10

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

Sift4G

Benign

0.41

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

Polyphen

0.049

B;B;D;D;.;D;.;B;B;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.58

MutPred

0.19

.;.;.;Loss of phosphorylation at S535 (P = 0.0534);.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;

MVP

0.75

MPC

0.18

ClinPred

0.11

GERP RS

3.9

Varity_R

0.10

gMVP

0.17

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