16-28392119-T-C

Variant names:

• chr16-28392119-T-C
• rs1422877931
• NM_001317857.2:c.800A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001317857.2(EIF3CL):​c.800A>G​(p.Lys267Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000039 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF3CL NM_001317857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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=0.10584757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3CL	NM_001317857.2	c.800A>G	p.Lys267Arg	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.800A>G	p.Lys267Arg	missense_variant	Exon 9 of 21	1	NM_001317857.2	ENSP00000370258.5
EIF3CL	ENST00000398944.7	c.800A>G	p.Lys267Arg	missense_variant	Exon 9 of 21	5		ENSP00000381917.3

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000385 AC: 2 AN: 519204 Hom.: 1 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 266440

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: 0.00000555

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.800A>G (p.K267R) alteration is located in exon 9 (coding exon 8) of the EIF3CL gene. This alteration results from a A to G substitution at nucleotide position 800, causing the lysine (K) at amino acid position 267 to be replaced by an arginine (R). 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	Benign	0.076
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.080
Sift	Benign	0.43	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.047	B;B
Vest4		0.21
MutPred		0.51		Loss of ubiquitination at K267 (P = 0.0192);Loss of ubiquitination at K267 (P = 0.0192);
MVP		0.040
ClinPred		0.49	T
GERP RS		3.8
Varity_R		0.13
gMVP		0.055

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: rs1422877931; hg19: chr16-28403440;