17-7311089-G-A

Position:

• chr17-7311089-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP2

The NM_001970.5(EIF5A):​c.237G>A​(p.Met79Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF5A NM_001970.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.43

Genes affected

EIF5A (HGNC:3300): (eukaryotic translation initiation factor 5A) Enables U6 snRNA binding activity and protein N-terminus binding activity. Involved in several processes, including cellular response to virus; positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; and tumor necrosis factor-mediated signaling pathway. Located in annulate lamellae; cytoplasm; and nucleus. Part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a region_of_interest Interaction with DOHH (size 70) in uniprot entity IF5A1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001970.5
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EIF5A. . Gene score misZ 2.407 (greater than the threshold 3.09). Trascript score misZ 4.4819 (greater than threshold 3.09). GenCC has associacion of gene with Faundes-Banka syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF5A	NM_001970.5	c.237G>A	p.Met79Ile	missense_variant	3/6	ENST00000336458.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF5A	ENST00000336458.13	c.237G>A	p.Met79Ile	missense_variant	3/6	1	NM_001970.5	P1

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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 07, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	.;D;D;.;D;D;D;T;D
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;.;.;D;.;.;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;M;.;M;M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.5	D;D;.;.;.;D;.;.;D
REVEL	Uncertain	0.29
Sift	Benign	0.045	D;T;.;.;.;T;.;.;T
Sift4G	Benign	0.25	T;T;T;T;T;T;T;T;T
Polyphen		0.021	B;B;B;.;B;B;B;.;B
Vest4		0.72
MutPred		0.43		.;Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);Loss of catalytic residue at M79 (P = 0.0419);
MVP		0.89
MPC		2.2
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-7214408;