3-71690113-GAC-AAT

Variant names:

• chr3-71690113-GAC-AAT
• NM_001134651.2:c.523_525delGTCinsATT
• EIF4E3 p.Val175Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001134651.2(EIF4E3):​c.523_525delGTCinsATT​(p.Val175Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF4E3 NM_001134651.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.73
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.523_525delGTCinsATT	p.Val175Ile	missense	N/A	NP_001128123.1	Q8N5X7-1
	EIF4E3	NM_001134649.3		c.205_207delGTCinsATT	p.Val69Ile	missense	N/A	NP_001128121.1	Q8N5X7-2
	EIF4E3	NM_001134650.1		c.205_207delGTCinsATT	p.Val69Ile	missense	N/A	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.523_525delGTCinsATT	p.Val175Ile	missense	N/A	ENSP00000393324.2	Q8N5X7-1
	EIF4E3	ENST00000295612.7	TSL:1	c.205_207delGTCinsATT	p.Val69Ile	missense	N/A	ENSP00000295612.3	Q8N5X7-2
	EIF4E3	ENST00000421769.6	TSL:1	c.205_207delGTCinsATT	p.Val69Ile	missense	N/A	ENSP00000411762.2	Q8N5X7-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-71739264;