NM_001135553.4:c.1169G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135553.4(MKNK1):​c.1169G>C​(p.Arg390Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R390H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MKNK1
NM_001135553.4 missense

Scores

1
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

Publications

0 publications found
Variant links:
Genes affected
MKNK1 (HGNC:7110): (MAPK interacting serine/threonine kinase 1) This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]
MKNK1-AS1 (HGNC:44129): (MKNK1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
MKNK1NM_001135553.4 linkc.1169G>C p.Arg390Pro missense_variant Exon 13 of 13 ENST00000371945.10 NP_001129025.2 Q9BUB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MKNK1ENST00000371945.10 linkc.1169G>C p.Arg390Pro missense_variant Exon 13 of 13 1 NM_001135553.4 ENSP00000361013.5 A0A499FJN1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461746
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727184
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53342
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111970
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.092
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;.;T;.;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D;D;D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.43
T;T;T;T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
2.0
M;.;.;.;.
PhyloP100
3.2
PrimateAI
Uncertain
0.73
T
REVEL
Benign
0.21
Sift4G
Benign
0.072
.;.;T;.;.
Polyphen
0.97
D;P;P;.;.
Vest4
0.37
MutPred
0.29
Loss of MoRF binding (P = 0.0065);.;.;.;.;
MVP
0.85
MPC
1.1
ClinPred
0.94
D
GERP RS
3.5
Varity_R
0.90
gMVP
0.67
Mutation Taster
=50/50

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

Other links and lift over

dbSNP: rs776962696; hg19: chr1-47024317; API