8-108248678-G-C

Variant names:

• chr8-108248678-G-C
• rs762263369
• ENST00000521440.6:c.-294C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000521440.6(EIF3E):​c.-294C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000205 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EIF3E ENST00000521440.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73
• Publications: 1 publications found

Genes affected

EIF3E (HGNC:3277): (eukaryotic translation initiation factor 3 subunit E) Enables protein N-terminus binding activity. Contributes to translation initiation factor activity. Involved in positive regulation of mRNA binding activity; regulation of gene expression; and translational initiation. Located in cytosol and nucleus. Part of eukaryotic translation initiation factor 3 complex. Colocalizes with PML body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521440.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3E	NM_001568.3	MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 13	NP_001559.1	P60228

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3E	ENST00000521440.6	TSL:1	c.-294C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000430152.2	H0YBR5
	EIF3E	ENST00000220849.10	TSL:1 MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 13	ENSP00000220849.5	P60228
	EIF3E	ENST00000518442.5	TSL:1	c.25C>G	p.Arg9Gly	missense	Exon 1 of 5	ENSP00000504091.1	A0A7I2V570

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.18
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.050	T
Polyphen		0.028	B
Vest4		0.56
MutPred		0.68		Loss of stability (P = 0.043)
MVP		0.69
MPC		1.2
ClinPred		0.99	D
GERP RS		5.3
PromoterAI		-0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.81
Mutation Taster		=42/58	disease causing

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

Other links and lift over

dbSNP: rs762263369; hg19: chr8-109260907;