16-28392002-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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. 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
• Clinical Significance: Not reported in ClinVar
• 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=0.11754757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3CL	NM_001317857.2	c.917G>C	p.Arg306Pro	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>C	p.Arg306Pro	missense_variant	Exon 9 of 21	1	NM_001317857.2	ENSP00000370258.5
EIF3CL	ENST00000398944.7	c.917G>C	p.Arg306Pro	missense_variant	Exon 9 of 21	5		ENSP00000381917.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00000840 AC: 1 AN: 119062 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 63612

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 SAS exome AF: 0.0000848

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: 3 AN: 359256 Hom.: 1 Cov.: 6 AF XY: 0.0000105 AC XY: 2 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: 0.0000708

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ExAC AF: 0.00000920 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Benign	0.91
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.069
Sift	Benign	0.076	T;T
Sift4G	Uncertain	0.053	T;T
Polyphen		0.21	B;B
Vest4		0.31
MutPred		0.58		Loss of MoRF binding (P = 0.0035);Loss of MoRF binding (P = 0.0035);
MVP		0.16
ClinPred		0.14	T
GERP RS		1.7
Varity_R		0.49
gMVP		0.25

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;