chr3-71693926-C-G

Variant names:

• chr3-71693926-C-G
• NM_001134651.2:c.421G>C

Variant summary

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

The NM_001134651.2(EIF4E3):​c.421G>C​(p.Glu141Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,292 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EIF4E3 NM_001134651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50
• Publications: 0 publications found

Genes affected

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

ENSG00000285708 (HGNC:):

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: NM_001134651.2. 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
	EIF4E3	NM_001134651.2	MANE Select	c.421G>C	p.Glu141Gln	missense	Exon 5 of 7	NP_001128123.1	Q8N5X7-1
	EIF4E3	NM_001134649.3		c.103G>C	p.Glu35Gln	missense	Exon 6 of 8	NP_001128121.1	Q8N5X7-2
	EIF4E3	NM_001134650.1		c.103G>C	p.Glu35Gln	missense	Exon 6 of 8	NP_001128122.1	Q8N5X7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E3	ENST00000425534.8	TSL:2 MANE Select	c.421G>C	p.Glu141Gln	missense	Exon 5 of 7	ENSP00000393324.2	Q8N5X7-1
	EIF4E3	ENST00000295612.7	TSL:1	c.103G>C	p.Glu35Gln	missense	Exon 6 of 8	ENSP00000295612.3	Q8N5X7-2
	EIF4E3	ENST00000421769.6	TSL:1	c.103G>C	p.Glu35Gln	missense	Exon 6 of 8	ENSP00000411762.2	Q8N5X7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431292 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709500

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.00 AC: 0 AN: 40682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25556

East Asian (EAS) AF: 0.00 AC: 0 AN: 38914

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096504

Other (OTH) AF: 0.00 AC: 0 AN: 59166

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.60		Gain of MoRF binding (P = 0.0342)
MVP		0.78
MPC		0.21
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.52
gMVP		0.63
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

hg19: chr3-71743077;