19-38626028-C-G

Variant names:

• chr19-38626028-C-G
• NM_013234.4:c.280C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013234.4(EIF3K):​c.280C>G​(p.Gln94Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF3K NM_013234.4 missense, splice_region
• Scores: Splicing: ADA: 0.3735
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61

Genes affected

EIF3K (HGNC:24656): (eukaryotic translation initiation factor 3 subunit K) The 700-kD eukaryotic translation initiation factor-3 (eIF3) is the largest eIF and contains at least 12 subunits, including EIF2S12. eIF3 plays an essential role in translation by binding directly to the 40S ribosomal subunit and promoting formation of the 40S preinitiation complex (Mayeur et al., 2003 [PubMed 14519125]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3K	NM_013234.4	c.280C>G	p.Gln94Glu	missense_variant, splice_region_variant	Exon 4 of 8	ENST00000248342.9	NP_037366.1
EIF3K	NM_001300992.2	c.280C>G	p.Gln94Glu	missense_variant, splice_region_variant	Exon 4 of 7		NP_001287921.1
EIF3K	NM_001308393.2	c.19C>G	p.Gln7Glu	missense_variant, splice_region_variant	Exon 4 of 8		NP_001295322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3K	ENST00000248342.9	c.280C>G	p.Gln94Glu	missense_variant, splice_region_variant	Exon 4 of 8	1	NM_013234.4	ENSP00000248342.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.280C>G (p.Q94E) alteration is located in exon 4 (coding exon 4) of the EIF3K gene. This alteration results from a C to G substitution at nucleotide position 280, causing the glutamine (Q) at amino acid position 94 to be replaced by a glutamic acid (E). 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	0.33
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;T;.;.;.;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	.;.;M;.;.;M;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.4	.;.;N;N;.;N;.;.
REVEL	Uncertain	0.43
Sift	Benign	0.032	.;.;D;D;.;D;.;.
Sift4G	Benign	0.31	T;T;T;T;T;T;T;T
Polyphen		0.89, 0.99	.;.;P;D;.;.;.;.
Vest4		0.62
MutPred		0.72		.;.;Gain of disorder (P = 0.0888);.;Gain of disorder (P = 0.0888);Gain of disorder (P = 0.0888);.;Gain of disorder (P = 0.0888);
MVP		0.38
MPC		0.46
ClinPred		0.72	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.37
dbscSNV1_RF	Benign	0.40
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-39116668;