chr3-170893377-T-C

Variant names:

• chr3-170893377-T-C
• rs984933878
• NM_020390.6:c.445A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020390.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF5A2	NM_020390.6	MANE Select	c.445A>G	p.Ile149Val	missense	Exon 5 of 5	NP_065123.1	Q9GZV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF5A2	ENST00000295822.7	TSL:1 MANE Select	c.445A>G	p.Ile149Val	missense	Exon 5 of 5	ENSP00000295822.2	Q9GZV4
	EIF5A2	ENST00000931515.1		c.340A>G	p.Ile114Val	missense	Exon 4 of 4	ENSP00000601574.1
	EIF5A2	ENST00000487522.5	TSL:3	c.313A>G	p.Ile105Val	missense	Exon 4 of 4	ENSP00000418305.1	C9J7B5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.17
Eigen_PC	Benign	0.095
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N
PhyloP100		5.0
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.036
Sift	Benign	1.0	T
Sift4G	Benign	0.78	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
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs984933878; hg19: chr3-170611166;