16-28392002-C-A

Variant names:

• chr16-28392002-C-A
• rs767204384
• NM_001317857.2:c.917G>T

Variant summary

Our verdict is Likely benign. Variant got -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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF3CL NM_001317857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.51

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13334435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3CL	NM_001317857.2	c.917G>T	p.Arg306Leu	missense_variant	Exon 9 of 21	ENST00000380876.5	NP_001304786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3CL	ENST00000380876.5	c.917G>T	p.Arg306Leu	missense_variant	Exon 9 of 21	1	NM_001317857.2	ENSP00000370258.5
EIF3CL	ENST00000398944.7	c.917G>T	p.Arg306Leu	missense_variant	Exon 9 of 21	5		ENSP00000381917.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 359256 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 190524

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.917G>T (p.R306L) alteration is located in exon 9 (coding exon 8) of the EIF3CL gene. This alteration results from a G to T substitution at nucleotide position 917, causing the arginine (R) at amino acid position 306 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;.
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.074
Sift	Benign	0.084	T;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.12	B;B
Vest4		0.31
MutPred		0.65		Loss of MoRF binding (P = 0.0122);Loss of MoRF binding (P = 0.0122);
MVP		0.26
ClinPred		0.75	D
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

LitVar

Other links and lift over

dbSNP: rs767204384; hg19: chr16-28403323;