chr22-31442114-G-C

Position:

• chr22-31442114-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019843.4(EIF4ENIF1):​c.2211C>G​(p.Asn737Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF4ENIF1 NM_019843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.794

Genes affected

EIF4ENIF1 (HGNC:16687): (eukaryotic translation initiation factor 4E nuclear import factor 1) The protein encoded by this gene is a nucleocytoplasmic shuttle protein for the translation initiation factor eIF4E. This shuttle protein interacts with the importin alpha-beta complex to mediate nuclear import of eIF4E. It is predominantly cytoplasmic; its own nuclear import is regulated by a nuclear localization signal and nuclear export signals. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

EIF4ENIF1 (HGNC:):

DRG1 (HGNC:3029): (developmentally regulated GTP binding protein 1) Enables several functions, including GTPase activity; identical protein binding activity; and potassium ion binding activity. Involved in positive regulation of microtubule polymerization and regulation of mitotic spindle assembly. Located in cytosol and nuclear body. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057461113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4ENIF1	NM_019843.4	c.2211C>G	p.Asn737Lys	missense_variant	17/19	ENST00000330125.10	NP_062817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4ENIF1	ENST00000330125.10	c.2211C>G	p.Asn737Lys	missense_variant	17/19	1	NM_019843.4	ENSP00000328103.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.2211C>G (p.N737K) alteration is located in exon 17 (coding exon 16) of the EIF4ENIF1 gene. This alteration results from a C to G substitution at nucleotide position 2211, causing the asparagine (N) at amino acid position 737 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.22	.;T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.66	T;.;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.35	N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.046	D;D;D;D
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.090, 0.0	.;B;B;B
Vest4		0.20
MutPred		0.15		.;Gain of ubiquitination at N737 (P = 0.0029);Gain of ubiquitination at N737 (P = 0.0029);.;
MVP		0.26
MPC		0.17
ClinPred		0.14	T
GERP RS		1.8
Varity_R		0.075
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-31838100;