dbSNP rs1363069984: EIF3K:p.Leu162Val (chr19-38632663-C-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_013234.4(EIF3K):c.484C>G(p.Leu162Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L162F) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Variant links:

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]

EIF3K links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3K	NM_013234.4 link	c.484C>G	p.Leu162Val	missense_variant	Exon 6 of 8	ENST00000248342.9	NP_037366.1	Q9UBQ5-1
EIF3K	NM_001308393.2 link	c.223C>G	p.Leu75Val	missense_variant	Exon 6 of 8		NP_001295322.1	K7EK53
EIF3K	NM_001300992.2 link	c.421+167C>G		intron_variant	Intron 5 of 6		NP_001287921.1	K7ERF1U3LUI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3K	ENST00000248342.9 link	c.484C>G	p.Leu162Val	missense_variant	Exon 6 of 8	1	NM_013234.4	ENSP00000248342.3		Q9UBQ5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250108

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T;.;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.059

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.3

.;.;M;.;M;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.6

.;.;D;D;D;.

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0030

.;.;D;D;D;.

Sift4G

Uncertain

0.0080

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D;.;.

Vest4

0.83

MutPred

0.88

.;.;Gain of catalytic residue at L162 (P = 0.1103);.;Gain of catalytic residue at L162 (P = 0.1103);.;

MVP

0.69

MPC

1.2

ClinPred

0.90

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over