Variant 15-44537347-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003758.4(EIF3J):c.67G>A(p.Asp23Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000638 in 1,566,558 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

EIF3J
NM_003758.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

Variant links:

Genes affected

EIF3J (HGNC:3270): (eukaryotic translation initiation factor 3 subunit J) This gene encodes a core subunit of the eukaryotic initiation factor 3 complex, which participates in the initiation of translation by aiding in the recruitment of protein and mRNA components to the 40S ribosome. There are pseudogenes for this gene on chromosomes 1, 3, and 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

EIF3J links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06453368).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3J	NM_003758.4 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	2/8	ENST00000261868.10	NP_003749.2	O75822-1A0A024R5S5
EIF3J	NM_001284336.2 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	2/6		NP_001271265.1	O75822-3
EIF3J	NM_001284335.2 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	2/7		NP_001271264.1	O75822-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EIF3J	ENST00000261868.10 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	2/8	1	NM_003758.4	ENSP00000261868.5	O75822-1
EIF3J	ENST00000424492.7 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	2/6	4		ENSP00000414548.3	O75822-3
EIF3J	ENST00000535391.5 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	2/7	2		ENSP00000440221.1	O75822-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152114

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:

0.000386

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

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

172824

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

92820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000611

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:

0.00000566

AC:

AN:

1414328

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

699076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000188

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000855

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 22, 2023

The c.67G>A (p.D23N) alteration is located in exon 2 (coding exon 2) of the EIF3J gene. This alteration results from a G to A substitution at nucleotide position 67, causing the aspartic acid (D) at amino acid position 23 to be replaced by an asparagine (N). 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

0.19

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.59

CADD

Pathogenic

DANN

Benign

0.87

DEOGEN2

Benign

0.019

T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.84

T;T;T

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.19

B;.;.

Vest4

0.22

MutPred

0.40

Gain of methylation at R26 (P = 0.0992);Gain of methylation at R26 (P = 0.0992);Gain of methylation at R26 (P = 0.0992);

MVP

0.28

MPC

0.32

ClinPred

0.17

GERP RS

4.4

Varity_R

0.21

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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