1-32226185-C-T

Variant names:

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

Variant summary

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

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]

MTMR9LP (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39459193).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003757.4. 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
	EIF3I	NM_003757.4	MANE Select	c.265C>T	p.Leu89Phe	missense	Exon 5 of 11	NP_003748.1	Q13347
	EIF3I	NM_001394168.1		c.265C>T	p.Leu89Phe	missense	Exon 5 of 12	NP_001381097.1	A0A7I2YQI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3I	ENST00000677711.2	MANE Select	c.265C>T	p.Leu89Phe	missense	Exon 5 of 11	ENSP00000504061.1	Q13347
	EIF3I	ENST00000373586.2	TSL:1	c.265C>T	p.Leu89Phe	missense	Exon 5 of 11	ENSP00000362688.2	A0A7P0MRT9
	EIF3I	ENST00000678063.1		c.265C>T	p.Leu89Phe	missense	Exon 5 of 12	ENSP00000503706.1	A0A7I2YQI2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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	0.13
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.023	D
Sift4G	Benign	0.075	T
Polyphen		0.0020	B
Vest4		0.26
MutPred		0.41		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
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

hg19: chr1-32691786; COSMIC: COSV59085713; COSMIC: COSV59085713;