NM_013234.4:c.140A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_013234.4(EIF3K):​c.140A>C​(p.Asn47Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,636 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. N47S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

EIF3K
NM_013234.4 missense

Scores

5
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF3KNM_013234.4 linkc.140A>C p.Asn47Thr missense_variant Exon 2 of 8 ENST00000248342.9 NP_037366.1 Q9UBQ5-1
EIF3KNM_001300992.2 linkc.140A>C p.Asn47Thr missense_variant Exon 2 of 7 NP_001287921.1 K7ERF1U3LUI4
EIF3KNM_001308393.2 linkc.-122A>C 5_prime_UTR_variant Exon 2 of 8 NP_001295322.1 K7EK53

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF3KENST00000248342.9 linkc.140A>C p.Asn47Thr missense_variant Exon 2 of 8 1 NM_013234.4 ENSP00000248342.3 Q9UBQ5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251030
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135648
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461636
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
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
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Benign
-0.0078
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;.;.;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.92
D;D;D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Pathogenic
3.0
M;.;M;.
PrimateAI
Pathogenic
0.80
D
PROVEAN
Pathogenic
-5.2
D;.;D;.
REVEL
Uncertain
0.50
Sift
Benign
0.060
T;.;D;.
Sift4G
Uncertain
0.042
D;T;D;D
Polyphen
1.0
D;.;.;.
Vest4
0.87
MutPred
0.79
Gain of ubiquitination at K52 (P = 0.1047);Gain of ubiquitination at K52 (P = 0.1047);Gain of ubiquitination at K52 (P = 0.1047);Gain of ubiquitination at K52 (P = 0.1047);
MVP
0.73
MPC
0.99
ClinPred
0.99
D
GERP RS
3.4
Varity_R
0.79
gMVP
0.78

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

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

Other links and lift over

dbSNP: rs149062652; hg19: chr19-39111057; API