Variant 10-79512749-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001099692.2(EIF5AL1):c.100A>G(p.Lys34Glu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF5AL1
NM_001099692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01

Variant links:

Genes affected

EIF5AL1 (HGNC:17419): (eukaryotic translation initiation factor 5A like 1) Predicted to enable translation elongation factor activity. Predicted to be involved in positive regulation of translational elongation. Predicted to be located in endoplasmic reticulum membrane. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

EIF5AL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40210944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF5AL1	NM_001099692.2 linkuse as main transcript	c.100A>G	p.Lys34Glu	missense_variant	1/1	ENST00000520547.4	NP_001093162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF5AL1	ENST00000520547.4 linkuse as main transcript	c.100A>G	p.Lys34Glu	missense_variant	1/1		NM_001099692.2	ENSP00000430706	P1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150784

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:

0.0000296

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.0000365

AC:

AN:

164368

Hom.:

AF XY:

0.0000456

AC XY:

AN XY:

87808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000657

AC:

AN:

1430384

Hom.:

Cov.:

AF XY:

0.0000661

AC XY:

AN XY:

711382

show subpopulations

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:

0.0000791

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000199

AC:

AN:

150784

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73576

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:

0.0000296

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000886

AC:

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

May 10, 2024

The c.100A>G (p.K34E) alteration is located in exon 1 (coding exon 1) of the EIF5AL1 gene. This alteration results from a A to G substitution at nucleotide position 100, causing the lysine (K) at amino acid position 34 to be replaced by a glutamic acid (E). 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

0.64

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Benign

0.18

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0066

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.42

MutPred

0.45

Loss of MoRF binding (P = 0.0052);

MVP

0.29

ClinPred

0.65

GERP RS

1.3

Varity_R

0.31

gMVP

0.49

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