chr3-170893377-T-C

Position:

• chr3-170893377-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020390.6(EIF5A2):​c.445A>G​(p.Ile149Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF5A2 NM_020390.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

Genes affected

EIF5A2 (HGNC:3301): (eukaryotic translation initiation factor 5A2) Predicted to enable translation elongation factor activity. Predicted to be involved in positive regulation of translational elongation. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13548785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF5A2	NM_020390.6	c.445A>G	p.Ile149Val	missense_variant	5/5	ENST00000295822.7	NP_065123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF5A2	ENST00000295822.7	c.445A>G	p.Ile149Val	missense_variant	5/5	1	NM_020390.6	ENSP00000295822	P1
EIF5A2	ENST00000487522.5	c.313A>G	p.Ile105Val	missense_variant	4/4	3		ENSP00000418305
EIF5A2	ENST00000474096.5	c.*87A>G		3_prime_UTR_variant	5/5	4		ENSP00000418370
EIF5A2	ENST00000460117.5	n.277A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 17, 2021

The c.445A>G (p.I149V) alteration is located in exon 5 (coding exon 4) of the EIF5A2 gene. This alteration results from a A to G substitution at nucleotide position 445, causing the isoleucine (I) at amino acid position 149 to be replaced by a valine (V). 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	0.062
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.095
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.036
Sift	Benign	1.0	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.0040	B;.
Vest4		0.39
MutPred		0.23		Gain of disorder (P = 0.052);.;
MVP		0.48
MPC		0.49
ClinPred		0.39	T
GERP RS		6.0
Varity_R		0.081
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs984933878; hg19: chr3-170611166;