1-32226480-T-C

Position:

• chr1-32226480-T-C

Variant summary

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

The NM_003757.4(EIF3I):​c.478T>C​(p.Cys160Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,442,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EIF3I NM_003757.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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]

EIF3I (HGNC:):

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=0.266684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3I	NM_003757.4	c.478T>C	p.Cys160Arg	missense_variant	6/11	ENST00000677711.2	NP_003748.1
EIF3I	NM_001394168.1	c.478T>C	p.Cys160Arg	missense_variant	6/12		NP_001381097.1
EIF3I	XM_024450518.2	c.129+2005T>C		intron_variant			XP_024306286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3I	ENST00000677711.2	c.478T>C	p.Cys160Arg	missense_variant	6/11		NM_003757.4	ENSP00000504061.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442058 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716480

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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

Mar 24, 2023

The c.478T>C (p.C160R) alteration is located in exon 6 (coding exon 6) of the EIF3I gene. This alteration results from a T to C substitution at nucleotide position 478, causing the cysteine (C) at amino acid position 160 to be replaced by an arginine (R). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.27
Sift	Benign	0.13	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.48
MutPred		0.63		Gain of disorder (P = 0.0308);
MVP		0.68
MPC		0.77
ClinPred		0.60	D
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.33
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr1-32692081; COSMIC: COSV59084159; COSMIC: COSV59084159;