NM_001317857.2:c.890A>G

Variant names:

• chr16-28392029-T-C
• rs200374164
• NM_001317857.2:c.890A>G

Variant summary

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

The NM_001317857.2(EIF3CL):​c.890A>G​(p.Asn297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000061 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF3CL NM_001317857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• Publications: 0 publications found

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]

ENSG00000309023 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.104025126).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3CL	NM_001317857.2	MANE Select	c.890A>G	p.Asn297Ser	missense	Exon 9 of 21	NP_001304786.1	B5ME19
	EIF3CL	NM_001099661.2		c.890A>G	p.Asn297Ser	missense	Exon 9 of 21	NP_001093131.1	B5ME19
	EIF3CL	NM_001317856.1		c.890A>G	p.Asn297Ser	missense	Exon 9 of 21	NP_001304785.1	B5ME19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3CL	ENST00000380876.5	TSL:1 MANE Select	c.890A>G	p.Asn297Ser	missense	Exon 9 of 21	ENSP00000370258.5	B5ME19
	EIF3CL	ENST00000398944.7	TSL:5	c.890A>G	p.Asn297Ser	missense	Exon 9 of 21	ENSP00000381917.3	B5ME19
	EIF3CL	ENST00000864343.1		c.890A>G	p.Asn297Ser	missense	Exon 8 of 20	ENSP00000534402.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000614 AC: 2 AN: 32584 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18258

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6744

American (AMR) AF: 0.00 AC: 0 AN: 2516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 238

East Asian (EAS) AF: 0.00 AC: 0 AN: 794

South Asian (SAS) AF: 0.00 AC: 0 AN: 4192

European-Finnish (FIN) AF: 0.000505 AC: 2 AN: 3958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12604

Other (OTH) AF: 0.00 AC: 0 AN: 1436

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000394 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.2
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.039
Sift	Benign	0.36	T
Sift4G	Benign	0.81	T
Polyphen		0.0080	B
Vest4		0.20
MutPred		0.32		Gain of phosphorylation at N297 (P = 0.0013)
MVP		0.055
ClinPred		0.58	D
GERP RS		3.8
Varity_R		0.092
gMVP		0.020
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200374164; hg19: chr16-28403350;