chr1-32228580-G-T

Position:

• chr1-32228580-G-T

Variant summary

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

The NM_003757.4(EIF3I):​c.610G>T​(p.Val204Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EIF3I NM_003757.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22930035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3I	NM_003757.4	c.610G>T	p.Val204Leu	missense_variant	7/11	ENST00000677711.2	NP_003748.1
EIF3I	NM_001394168.1	c.610G>T	p.Val204Leu	missense_variant	7/12		NP_001381097.1
EIF3I	XM_024450518.2	c.211G>T	p.Val71Leu	missense_variant	4/8		XP_024306286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3I	ENST00000677711.2	c.610G>T	p.Val204Leu	missense_variant	7/11		NM_003757.4	ENSP00000504061.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

May 08, 2023

The c.610G>T (p.V204L) alteration is located in exon 7 (coding exon 7) of the EIF3I gene. This alteration results from a G to T substitution at nucleotide position 610, causing the valine (V) at amino acid position 204 to be replaced by a leucine (L). 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	0.39
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.35
MutPred		0.63		Loss of catalytic residue at V204 (P = 0.1128);
MVP		0.58
MPC		0.45
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs11554220; hg19: chr1-32694181;