chr2-99363802-G-T

Position:

• chr2-99363802-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015904.4(EIF5B):​c.1077G>T​(p.Lys359Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF5B NM_015904.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

Genes affected

EIF5B (HGNC:30793): (eukaryotic translation initiation factor 5B) Accurate initiation of translation in eukaryotes is complex and requires many factors, some of which are composed of multiple subunits. The process is simpler in prokaryotes which have only three initiation factors (IF1, IF2, IF3). Two of these factors are conserved in eukaryotes: the homolog of IF1 is eIF1A and the homolog of IF2 is eIF5B. This gene encodes eIF5B. Factors eIF1A and eIF5B interact on the ribosome along with other initiation factors and GTP to position the initiation methionine tRNA on the start codon of the mRNA so that translation initiates accurately. [provided by RefSeq, Jul 2008]

EIF5B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26440373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF5B	NM_015904.4	c.1077G>T	p.Lys359Asn	missense_variant	5/24	ENST00000289371.11	NP_056988.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF5B	ENST00000289371.11	c.1077G>T	p.Lys359Asn	missense_variant	5/24	1	NM_015904.4	ENSP00000289371.5
EIF5B	ENST00000617677.1	c.1077G>T	p.Lys359Asn	missense_variant	5/25	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 30, 2024

The c.1077G>T (p.K359N) alteration is located in exon 5 (coding exon 5) of the EIF5B gene. This alteration results from a G to T substitution at nucleotide position 1077, causing the lysine (K) at amino acid position 359 to be replaced by an asparagine (N). 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.040	D;D
Polyphen		0.98	D;.
Vest4		0.51
MutPred		0.28		Loss of methylation at K359 (P = 0.0055);Loss of methylation at K359 (P = 0.0055);
MVP		0.48
MPC		0.35
ClinPred		0.87	D
GERP RS		-0.029
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.25
gMVP		0.070

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-99980265;