1-20817509-GGG-TAA

Variant names:

• chr1-20817509-GGG-TAA
• NM_001391906.1:c.4396_4398delCCCinsTTA
• EIF4G3 p.Pro1466Leu

Variant summary

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

The NM_001391906.1(EIF4G3):​c.4396_4398delCCCinsTTA​(p.Pro1466Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1466R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EIF4G3 NM_001391906.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.97
• Publications: 0 publications found

Genes affected

EIF4G3 (HGNC:3298): (eukaryotic translation initiation factor 4 gamma 3) The protein encoded by this gene is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. Interestingly, a microRNA (miR-520c-3p) has been found that negatively regulates synthesis of the encoded protein, and this leads to a global decrease in protein translation and cell proliferation. Therefore, this protein is a key component of the anti-tumor activity of miR-520c-3p. [provided by RefSeq, May 2016]

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_001391906.1. 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
	EIF4G3	NM_001391906.1	MANE Select	c.4396_4398delCCCinsTTA	p.Pro1466Leu	missense	N/A	NP_001378835.1	A0A8J9G7U8
	EIF4G3	NM_001391907.1		c.4486_4488delCCCinsTTA	p.Pro1496Leu	missense	N/A	NP_001378836.1
	EIF4G3	NM_001438678.1		c.4375_4377delCCCinsTTA	p.Pro1459Leu	missense	N/A	NP_001425607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4G3	ENST00000602326.6	TSL:1 MANE Select	c.4396_4398delCCCinsTTA	p.Pro1466Leu	missense	N/A	ENSP00000473510.2	A0A8J9G7U8
	EIF4G3	ENST00000400422.6	TSL:1	c.4336_4338delCCCinsTTA	p.Pro1446Leu	missense	N/A	ENSP00000383274.2	A0A0A0MSA7
	EIF4G3	ENST00000693470.1		c.5158_5160delCCCinsTTA	p.Pro1720Leu	missense	N/A	ENSP00000509295.1	A0A8I5KV92

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

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: chr1-21144002;