chr3-71725304-C-T

Variant names:

• chr3-71725304-C-T
• rs992895762
• NM_001134651.2:c.64G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001134651.2(EIF4E3):​c.64G>A​(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 988,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: EIF4E3 NM_001134651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.257
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15131238).

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.64G>A	p.Ala22Thr	missense	Exon 1 of 7	NP_001128123.1	Q8N5X7-1
	EIF4E3	NM_001134649.3		c.-143+3172G>A		intron	N/A	NP_001128121.1	Q8N5X7-2
	EIF4E3	NM_001134650.1		c.-143+3172G>A		intron	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.64G>A	p.Ala22Thr	missense	Exon 1 of 7	ENSP00000393324.2	Q8N5X7-1
	ENSG00000285708	ENST00000647725.1		c.-811+3172G>A		intron	N/A	ENSP00000497585.1
	EIF4E3	ENST00000295612.7	TSL:1	c.-143+3172G>A		intron	N/A	ENSP00000295612.3	Q8N5X7-2

Frequencies

GnomAD3 genomes AF: 0.0000547 AC: 8 AN: 146150 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000984

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 12 AN: 842488 Hom.: 0 Cov.: 18 AF XY: 0.0000230 AC XY: 9 AN XY: 390860

African (AFR) AF: 0.00 AC: 0 AN: 15884

American (AMR) AF: 0.00 AC: 0 AN: 1506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5552

East Asian (EAS) AF: 0.000698 AC: 3 AN: 4298

South Asian (SAS) AF: 0.000405 AC: 7 AN: 17266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 766104

Other (OTH) AF: 0.0000715 AC: 2 AN: 27988

GnomAD4 genome AF: 0.0000547 AC: 8 AN: 146242 Hom.: 0 Cov.: 31 AF XY: 0.0000983 AC XY: 7 AN XY: 71190

African (AFR) AF: 0.00 AC: 0 AN: 40840

American (AMR) AF: 0.00 AC: 0 AN: 14768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.000987 AC: 5 AN: 5064

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000304 AC: 2 AN: 65754

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

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	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.35	N
REVEL	Benign	0.10
Sift	Benign	0.56	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.52		Loss of helix (P = 0.0167)
MVP		0.30
MPC		0.025
ClinPred		0.21	T
GERP RS		0.96
PromoterAI		0.023	Neutral
Varity_R		0.031
gMVP		0.37
Mutation Taster		=90/10	polymorphism

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: rs992895762; hg19: chr3-71774455; COSMIC: COSV108087285;