Genetic Variant EIF3B:p.Ser64Ala (chr7-2355111-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037283.2(EIF3B):c.190T>G(p.Ser64Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. S64P) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF3B
NM_001037283.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

Publications

28 publications found

Variant links:

Genes affected

EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032348633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037283.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3B	NM_001037283.2	MANE Select	c.190T>G	p.Ser64Ala	missense	Exon 1 of 19	NP_001032360.1	P55884-1
EIF3B	NM_001362791.2		c.190T>G	p.Ser64Ala	missense	Exon 1 of 19	NP_001349720.1	P55884-1
EIF3B	NM_003751.4		c.190T>G	p.Ser64Ala	missense	Exon 1 of 19	NP_003742.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3B	ENST00000360876.9	TSL:1 MANE Select	c.190T>G	p.Ser64Ala	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
EIF3B	ENST00000397011.2	TSL:1	c.190T>G	p.Ser64Ala	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
EIF3B	ENST00000899983.1		c.190T>G	p.Ser64Ala	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

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

AF:

0.00

AC:

AN:

1219846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

595558

African (AFR)

AF:

0.00

AC:

AN:

23864

American (AMR)

AF:

0.00

AC:

AN:

10638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17294

East Asian (EAS)

AF:

0.00

AC:

AN:

27138

South Asian (SAS)

AF:

0.00

AC:

AN:

55538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3456

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1002948

Other (OTH)

AF:

0.00

AC:

AN:

49800

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

5356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.018

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.052

M_CAP

Benign

0.034

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.23

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.020

REVEL

Benign

0.0080

Sift

Benign

0.54

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.045

MutPred

0.21

Loss of phosphorylation at S64 (P = 0.0042)

MVP

0.19

MPC

0.31

ClinPred

0.032

GERP RS

0.18

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Varity_R

0.029

gMVP

0.12

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over