Genetic Variant EIF3CL:p.Arg306Leu (chr16-28392002-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001317857.2(EIF3CL):c.917G>T(p.Arg306Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R306W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF3CL
NM_001317857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Publications

0 publications found

Variant links:

Genes affected

EIF3CL (HGNC:26347): (eukaryotic translation initiation factor 3 subunit C like) The protein encoded by this gene is a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex. The encoded protein is nearly identical to another protein, eIF3c, from a related gene. The eIF3 complex binds the 40S ribosome and mRNAs to enable translation initiation. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

EIF3CL links:

ENSG00000309023 (HGNC:):

ENSG00000309023 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13334435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3CL	NM_001317857.2	MANE Select	c.917G>T	p.Arg306Leu	missense	Exon 9 of 21	NP_001304786.1	B5ME19
EIF3CL	NM_001099661.2		c.917G>T	p.Arg306Leu	missense	Exon 9 of 21	NP_001093131.1	B5ME19
EIF3CL	NM_001317856.1		c.917G>T	p.Arg306Leu	missense	Exon 9 of 21	NP_001304785.1	B5ME19

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3CL	ENST00000380876.5	TSL:1 MANE Select	c.917G>T	p.Arg306Leu	missense	Exon 9 of 21	ENSP00000370258.5	B5ME19
EIF3CL	ENST00000398944.7	TSL:5	c.917G>T	p.Arg306Leu	missense	Exon 9 of 21	ENSP00000381917.3	B5ME19
EIF3CL	ENST00000864343.1		c.917G>T	p.Arg306Leu	missense	Exon 8 of 20	ENSP00000534402.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

359256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

190524

African (AFR)

AF:

0.00

AC:

AN:

14124

American (AMR)

AF:

0.00

AC:

AN:

14454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4504

East Asian (EAS)

AF:

0.00

AC:

AN:

5582

South Asian (SAS)

AF:

0.00

AC:

AN:

42344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1828

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

240754

Other (OTH)

AF:

0.00

AC:

AN:

13130

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.025

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.64

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0090

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

2.5

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-2.3

REVEL

Benign

0.074

Sift

Benign

0.084

Sift4G

Uncertain

0.059

Polyphen

0.12

Vest4

0.31

MutPred

0.65

Loss of MoRF binding (P = 0.0122)

MVP

0.26

ClinPred

0.75

GERP RS

1.7

Varity_R

0.17

gMVP

0.17

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over