14-103339259-C-A

Variant names:

• chr14-103339259-C-A
• NM_001969.5:c.832C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001969.5(EIF5):​c.832C>A​(p.Leu278Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF5 NM_001969.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

Genes affected

EIF5 (HGNC:3299): (eukaryotic translation initiation factor 5) Eukaryotic translation initiation factor-5 (EIF5) interacts with the 40S initiation complex to promote hydrolysis of bound GTP with concomitant joining of the 60S ribosomal subunit to the 40S initiation complex. The resulting functional 80S ribosomal initiation complex is then active in peptidyl transfer and chain elongations (summary by Si et al., 1996 [PubMed 8663286]).[supplied by OMIM, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF5	NM_001969.5	c.832C>A	p.Leu278Ile	missense_variant	Exon 9 of 12	ENST00000216554.8	NP_001960.2
EIF5	NM_183004.5	c.832C>A	p.Leu278Ile	missense_variant	Exon 8 of 11		NP_892116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF5	ENST00000216554.8	c.832C>A	p.Leu278Ile	missense_variant	Exon 9 of 12	1	NM_001969.5	ENSP00000216554.3
EIF5	ENST00000392715.6	c.832C>A	p.Leu278Ile	missense_variant	Exon 8 of 11	1		ENSP00000376477.2
EIF5	ENST00000558506.1	c.832C>A	p.Leu278Ile	missense_variant	Exon 7 of 10	1		ENSP00000453743.1
EIF5	ENST00000561380.1	n.247C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.832C>A (p.L278I) alteration is located in exon 9 (coding exon 7) of the EIF5 gene. This alteration results from a C to A substitution at nucleotide position 832, causing the leucine (L) at amino acid position 278 to be replaced by an isoleucine (I). 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	0.32
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.040	D;D;D
Sift4G	Uncertain	0.050	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.66
MutPred		0.47		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);
MVP		0.72
ClinPred		0.97	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.34

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: chr14-103805596;