NM_013234.4:c.346G>C

Variant names:

• chr19-38626094-G-C
• NM_013234.4:c.346G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013234.4(EIF3K):​c.346G>C​(p.Ala116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. A116S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EIF3K NM_013234.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30784062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3K	NM_013234.4	c.346G>C	p.Ala116Pro	missense_variant	Exon 4 of 8	ENST00000248342.9	NP_037366.1
EIF3K	NM_001300992.2	c.346G>C	p.Ala116Pro	missense_variant	Exon 4 of 7		NP_001287921.1
EIF3K	NM_001308393.2	c.85G>C	p.Ala29Pro	missense_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.346G>C	p.Ala116Pro	missense_variant	Exon 4 of 8	1	NM_013234.4	ENSP00000248342.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727218

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.;T;.;.;.;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	.;.;L;.;.;L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	.;.;N;N;.;N;.;.
REVEL	Benign	0.21
Sift	Benign	0.27	.;.;T;T;.;T;.;.
Sift4G	Benign	0.27	T;T;T;T;T;T;T;T
Polyphen		0.14, 0.43	.;.;B;B;.;.;.;.
Vest4		0.71
MutPred		0.42		.;.;Loss of catalytic residue at A116 (P = 0.0398);.;Loss of catalytic residue at A116 (P = 0.0398);Loss of catalytic residue at A116 (P = 0.0398);.;Loss of catalytic residue at A116 (P = 0.0398);
MVP		0.34
MPC		0.55
ClinPred		0.44	T
GERP RS		3.3
Varity_R		0.47
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-39116734;