Genetic Variant EIF3CL:p.Arg306Pro (chr16-28392002-C-G) – 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>C(p.Arg306Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R306L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000084 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

EIF3CL
NM_001317857.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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=0.11754757).

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>C	p.Arg306Pro	missense	Exon 9 of 21	NP_001304786.1	B5ME19
EIF3CL	NM_001099661.2		c.917G>C	p.Arg306Pro	missense	Exon 9 of 21	NP_001093131.1	B5ME19
EIF3CL	NM_001317856.1		c.917G>C	p.Arg306Pro	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>C	p.Arg306Pro	missense	Exon 9 of 21	ENSP00000370258.5	B5ME19
EIF3CL	ENST00000398944.7	TSL:5	c.917G>C	p.Arg306Pro	missense	Exon 9 of 21	ENSP00000381917.3	B5ME19
EIF3CL	ENST00000864343.1		c.917G>C	p.Arg306Pro	missense	Exon 8 of 20	ENSP00000534402.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000840

AC:

AN:

119062

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000835

AC:

AN:

359256

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

190524

show subpopulations

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:

0.0000708

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000920

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.021

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.5

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.9

REVEL

Benign

0.069

Sift

Benign

0.076

Sift4G

Uncertain

0.053

Polyphen

0.21

Vest4

0.31

MutPred

0.58

Loss of MoRF binding (P = 0.0035)

MVP

0.16

ClinPred

0.14

GERP RS

1.7

Varity_R

0.49

gMVP

0.25

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over