1-32226185-C-T

Variant names:

• chr1-32226185-C-T
• NM_003757.4:c.265C>T

Variant summary

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

The NM_003757.4(EIF3I):​c.265C>T​(p.Leu89Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: EIF3I NM_003757.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01

Genes affected

EIF3I (HGNC:3272): (eukaryotic translation initiation factor 3 subunit I) Contributes to translation initiation factor activity. Involved in translational initiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.39459193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3I	NM_003757.4	c.265C>T	p.Leu89Phe	missense_variant	Exon 5 of 11	ENST00000677711.2	NP_003748.1
EIF3I	NM_001394168.1	c.265C>T	p.Leu89Phe	missense_variant	Exon 5 of 12		NP_001381097.1
EIF3I	XM_024450518.2	c.129+1710C>T		intron_variant	Intron 3 of 7		XP_024306286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3I	ENST00000677711.2	c.265C>T	p.Leu89Phe	missense_variant	Exon 5 of 11		NM_003757.4	ENSP00000504061.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.265C>T (p.L89F) alteration is located in exon 5 (coding exon 5) of the EIF3I gene. This alteration results from a C to T substitution at nucleotide position 265, causing the leucine (L) at amino acid position 89 to be replaced by a phenylalanine (F). 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	0.13
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.94	N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.075	T;T
Polyphen		0.0020	.;B
Vest4		0.26
MutPred		0.41		Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);
MVP		0.92
MPC		1.2
ClinPred		0.78	D
GERP RS		4.8
Varity_R		0.24
gMVP		0.20

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: chr1-32691786; COSMIC: COSV59085713; COSMIC: COSV59085713;